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1
Kuittinen, O. (Outi). "Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in hematological malignancies." Doctoral thesis, University of Oulu, 2003. http://urn.fi/urn:isbn:951426942X.
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Abstract
Gelatinases (MMP-2 and MMP-9) play a key role during
invasion and metastazising of malignant cells and they have been
shown to be associated to invasive phenotype and poor prognosis in
several solid tumours. However little is known about their role in
hematological malignancies. In the present work, gelatinase
expression and its clinicopathological correlations were studied
with immunohistochemical staining in 10 cases representing normal
bone marrow aspirate smears, 123 cases representing diagnostic
bone marrow samples of patients with different leukaemias (35 AML,
7 CLL, 6 CML, 75 ALL), 67 diagnostic paraffin-embedded lymph node
biopsies from patients with Hodgkin's lymphoma and 57 biopsies
from patients with non-Hodgkin's lymphomas. The lymphoma samples
were also stained with factor VIII antibody to evaluate the extent
of new vessel formation and the non-Hodgkin's lymphoma cases also
with tissue inhibitor of metalloproteinases -1 (TIMP-1) antibody.
CLL did not express either of the MMP enzymes, while CML in the
chronic phase expressed strongly both of the enzymes. In ALL,
gelatinase expression was weak and detectable in pediatric cases
in only 12.7% and in the adults in 65% of the cases. In adult ALL,
MMP-2 expression correlated strongly with an extramedullary and
invasive pattern of disease presentation. In AML MMP-2 positivity
had markedly favorable prognostic and predictive power. In
lymphoma studies, no correlations could be detected between
gelatinase expression and the clinical parameters of invasion.
MMP-9 positivity was related to the presence of B symptoms, which
difference was statistically significant in Hodgkin's lymphoma. In
Hodgkin's lymphoma, strong MMP-9 expression also implicated
decreased neovascularization. In both lymphoma types, strong MMP-9
expression correlated with unfavorable prognosis, which difference
was statistically significant in non-Hodgkin's lymphomas and
remained as a tendency in Hodgkin's lymphoma. MMP-2 had
statistically significant association with a favorable prognosis
in Hodgkin's lymphoma. Combination of the results of both
stainings further increased prognostic power. All together these
findings implicate that gelatinases could be used as prognostic
tools in AML and lymphomas albeit this needs to be verified in
larger materials.
2
College, of Law University of Arizona. "Law Record, Volume 9 No. 2." College of Law, University of Arizona (Tucson, AZ), 1988. http://hdl.handle.net/10150/612053.
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Gomes, Filho Robson Rodrigues [Verfasser], Thomas [Akademischer Betreuer] Fischer, and Larissa Moreira [Akademischer Betreuer] Viana. "Os missionários redentoristas alemães e as expectativas de progresso e modernização em Goiás (Brasil, 1894-1930) / Robson Rodrigues Gomes Filho ; Thomas Fischer, Larissa Moreira Viana." Eichstätt-Ingolstadt : Katholische Universität Eichstätt-Ingolstadt, 2018. http://d-nb.info/1168722934/34.
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Center, University of Arizona Water Resources Research, and Joe Gelt. "Arroyo Vol. 9 No. 2 (June 1996)." Water Resources Research Center, College of Agriculture, University of Arizona (Tucson, AZ), 1996. http://hdl.handle.net/10150/314803.
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Those who labor in the water resources field may at times feel their efforts to be slighted. Whereas military glories are marked by public monuments - statues, plaques, a cannon in the park - milestones in water resource developments are represented by laws, public policies, and court decisions. To small boys and most adults, a cannon in the park is more intriguing.
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Webber, Jason J. "Indiana Criminal Code 9-30-2-2 who does it protect? /." [Muncie, Ind.] : Ball State University, 2008. http://cardinalscholar.bsu.edu/375.
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Hein, Martin. "Regioselektive elektrophile Substitution von Decaboran B 10 H 14 : Darstellung und Reaktionsverhalten von B 9 Cl 9 und H 2 B 9 Cl 9 /." [S.l. : s.n.], 2002. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB10277650.
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Mazon, Talita [UNESP]. "Preparação e caracterização de filmes finos de 'BA''BI IND.2''TA IND.2''O IND.9(BBT)' e 'BA''BI IND.2''NB IND.2''O IND.9(BBN)'." Universidade Estadual Paulista (UNESP), 2001. http://hdl.handle.net/11449/105671.
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mazon_t_dr_araiq.pdf: 3325805 bytes, checksum: 1e16f8675a27d9c718c1eacce9a6a467 (MD5)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Nos últimos anos, filmes finos dos óxidos ferroelétricos de camadas de bismuto, também conhecidos como compostos pertencentes à família do Aurivillius, têm sido extensivamente estudados para aplicações em memórias ferroelétricas de acesso aleatório (FERAM). No entanto, muito pouco se sabe a respeito da preparação e propriedades dielétricas de filmes de BaBi2Ta2O9 (BBT) e BaBi2Nb2O9 (BBN), bem como a respeito da estrutura do BBT. Por isso, numa primeira etapa deste trabalho, pós de BBT foram preparados pelo método Pechini, para a determinação da estrutura. A formação de fases foi acompanhada por DRX. O pó calcinado a 800 oC por 2 horas e sinterizado a 850 oC por 4 horas apresentou 100% da fase BBT. A estrutura do BBT foi determinada pelo Método de Rietveld. Verificou-se que o BBT tem estrutura tetragonal com grupo espacial I4/mm, os cátions Ba e Bi compartilham ambos os sítios 2b e 4e. A fórmula (Ba0,70Bi0,30)(Bi1,64Ba0,36)Ta2O9 pode ser usada para escrever sua fórmula unitária. Numa segunda etapa, filmes finos de BBT e BBN foram preparados pelo método químico de Pechini. As soluções foram depositadas por “spin-coanting” em substratos de Pt/TiO2/SiO2/Si e rotacionados a 3000 rpm durante 30 segundos. Após a deposição os filmes foram tratados termicamente entre 600 e 800 oC sob atmosfera de oxigênio. Os filmes foram analisados por DRX, MEV, MFA, MET e propriedades elétricas. Os filmes preparados por este processamento apresentaram microestrutura heterogênea e piores propriedades dielétricas. Visando controlar a microestrutura e obter melhores propriedades dielétricas, foram feitas algumas modificações no processamento, tais como, adição de excesso de bismuto e adição de uma camada intermediária de tungstênio entre as camadas dos filmes de BBT ou BBN. Tanto a adição de excesso de bismuto como a utilização do dopante tungstênio...
In recent years the layered-structure perovskites, also known as Aurivillius compounds have attracted considerable attention for use in ferroelectric random access memories (FeRAM). However, there is little information available about the preparation and dielectric properties of BaBi2Ta2O9 (BBT) and BaBi2Nb2O9 (BBN) thin films, as well as, about the structure of BBT. Therefore, firstly BBT powders were prepared by Pechini method and the phase formation was verified by XRD. The powder calcined at 800 oC / 2 hours and sintered at 850 oC / 4h showed 100% of BBT phase. The structure of BBT was determined by the Rietveld method. BBT shows tetragonal structure (I4/mmm), and Ba and Bi share both the 2b and 4e sites. The (Ba0,70Bi0,30)(Bi1,64Ba0,36)Ta2O9 can be used to describe its unit formula. Secondly, thin films of BBT and BBN were prepared by Pechini method. They were deposited by spin coating over Pt/TiO2/SiO2/Si substrates followed by annealing under oxygen flux at different temperature. The thin films were analyzed by XRD, SEM, AFM, TEM and electric properties. The thin films showed heterogeneous microstructure and worst dielectric properties. Aiming to control the microstructure, it was done some modification during the process of preparation of BBT and BBN thin films. The use of Bi excess as well as the use of W6+ as dopant was favorable to control the microstructure and to obtain better dielectric properties. The best values to dielectric constant and dissipation factor were obtained for BBT thin films with addition of 5 wt% Bi excess heat annealed at 750 oC for 1 hour and BBN thin films with addition of 2 wt% Bi excess heat annealed at 700 oC for 1 hour The typical measured small signal dielectric constant and dissipation factor at 100 kHz were 210 and 0,025 for BBT and 356 and 0,023 for BBN, respectively...(Complete abstract click electronic access below)
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Mazon, Talita. "Preparação e caracterização de filmes finos de 'BA''BI IND.2''TA IND.2''O IND.9(BBT)' e 'BA''BI IND.2''NB IND.2''O IND.9(BBN)' /." Araraquara : [s.n.], 2001. http://hdl.handle.net/11449/105671.
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Orientador: Maria Aparecida ZagheteBanca: Carlos de Oliveria Paiva-Santos
Banca: Sidney José Lima Ribeiro
Banca: Ducinei Garcia
Banca: Antonio Carlos Hernandes
Resumo: Nos últimos anos, filmes finos dos óxidos ferroelétricos de camadas de bismuto, também conhecidos como compostos pertencentes à família do Aurivillius, têm sido extensivamente estudados para aplicações em memórias ferroelétricas de acesso aleatório (FERAM). No entanto, muito pouco se sabe a respeito da preparação e propriedades dielétricas de filmes de BaBi2Ta2O9 (BBT) e BaBi2Nb2O9 (BBN), bem como a respeito da estrutura do BBT. Por isso, numa primeira etapa deste trabalho, pós de BBT foram preparados pelo método Pechini, para a determinação da estrutura. A formação de fases foi acompanhada por DRX. O pó calcinado a 800 oC por 2 horas e sinterizado a 850 oC por 4 horas apresentou 100% da fase BBT. A estrutura do BBT foi determinada pelo Método de Rietveld. Verificou-se que o BBT tem estrutura tetragonal com grupo espacial I4/mm, os cátions Ba e Bi compartilham ambos os sítios 2b e 4e. A fórmula (Ba0,70Bi0,30)(Bi1,64Ba0,36)Ta2O9 pode ser usada para escrever sua fórmula unitária. Numa segunda etapa, filmes finos de BBT e BBN foram preparados pelo método químico de Pechini. As soluções foram depositadas por "spin-coanting" em substratos de Pt/TiO2/SiO2/Si e rotacionados a 3000 rpm durante 30 segundos. Após a deposição os filmes foram tratados termicamente entre 600 e 800 oC sob atmosfera de oxigênio. Os filmes foram analisados por DRX, MEV, MFA, MET e propriedades elétricas. Os filmes preparados por este processamento apresentaram microestrutura heterogênea e piores propriedades dielétricas. Visando controlar a microestrutura e obter melhores propriedades dielétricas, foram feitas algumas modificações no processamento, tais como, adição de excesso de bismuto e adição de uma camada intermediária de tungstênio entre as camadas dos filmes de BBT ou BBN. Tanto a adição de excesso de bismuto como a utilização do dopante tungstênio...(Resumo Completo, clicar acesso eletrônico abaixo)
Abstract: In recent years the layered-structure perovskites, also known as Aurivillius compounds have attracted considerable attention for use in ferroelectric random access memories (FeRAM). However, there is little information available about the preparation and dielectric properties of BaBi2Ta2O9 (BBT) and BaBi2Nb2O9 (BBN) thin films, as well as, about the structure of BBT. Therefore, firstly BBT powders were prepared by Pechini method and the phase formation was verified by XRD. The powder calcined at 800 oC / 2 hours and sintered at 850 oC / 4h showed 100% of BBT phase. The structure of BBT was determined by the Rietveld method. BBT shows tetragonal structure (I4/mmm), and Ba and Bi share both the 2b and 4e sites. The (Ba0,70Bi0,30)(Bi1,64Ba0,36)Ta2O9 can be used to describe its unit formula. Secondly, thin films of BBT and BBN were prepared by Pechini method. They were deposited by spin coating over Pt/TiO2/SiO2/Si substrates followed by annealing under oxygen flux at different temperature. The thin films were analyzed by XRD, SEM, AFM, TEM and electric properties. The thin films showed heterogeneous microstructure and worst dielectric properties. Aiming to control the microstructure, it was done some modification during the process of preparation of BBT and BBN thin films. The use of Bi excess as well as the use of W6+ as dopant was favorable to control the microstructure and to obtain better dielectric properties. The best values to dielectric constant and dissipation factor were obtained for BBT thin films with addition of 5 wt% Bi excess heat annealed at 750 oC for 1 hour and BBN thin films with addition of 2 wt% Bi excess heat annealed at 700 oC for 1 hour The typical measured small signal dielectric constant and dissipation factor at 100 kHz were 210 and 0,025 for BBT and 356 and 0,023 for BBN, respectively...(Complete abstract click electronic access below)
Doutor
9
Knaup, Martin [Verfasser]. "Die Begrenzung globaler Unternehmensleitung durch § 9 Absatz 2 Satz 2 StGB. / Martin Knaup." Berlin : Duncker & Humblot, 2011. http://d-nb.info/1238426174/34.
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Ruokolainen, H. (Henni). "The prognostic role of matrix metalloproteinase -2 and -9 (MMP-2, MMP-9) and their tissue inhibitors -1 and -2 (TIMP-1, TIMP-2) in head and neck squamous cell carcinoma." Doctoral thesis, University of Oulu, 2005. http://urn.fi/urn:isbn:9514279174.
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Abstract
Traditional clinicopathological factors are not accurate enough to predict the behavior of head and neck squamous cell carcinoma (HNSCC). The most powerful indicator of prognosis is the stage of the disease. New prognostic markers have, however, been searched for in order to better identify patient groups in need of different treatments or follow-up. Gelatinases (MMP-2, -9) are endopeptidases associated with tumor invasion and angiogenesis, and their tissue inhibitors (TIMP-1, -2) are also linked to cancer cell invasion and metastasis formation. In some cancer types they are even prognostic and relate with a more aggressive clinical course of the disease.
In the present work the expression and the clinical significance of tumor tissue and circulating immunoreactive proteins for MMP-2, -9, TIMP-1 and -2 were assessed in HNSCC. The study group included 74 patients with HNSCC and 44 healthy controls. The expression of immunoreactive proteins was examined in paraffin-embedded tumor sections by immunohistochemical staining using specific antibodies, and the pretreatment serum levels of those proteins were quantitatively measured by ELISA assay. Immunohistochemical overexpression of MMP-9 in tumor was for the first time found to predict the prognosis for shortened survival in HNSCC, the cause-specific survival rates being 45% and 92% and relapse-free survival being 42% and 79% in MMP-9 positive or negative cases, respectively. Additionally, tissue TIMP-1, MMP-2 and TIMP-2 positivity were all also linked with poorer survival of patients with HNSCC. However, these differences remained less distinct than with MMP-9. The expression of gelatinases and their inhibitors in tumor tissue was also an indicator for later lymph node or hematogenic relapses in HNSCC patients. Circulating MMP-9 and TIMP-1 levels were significantly higher in HNSCC patients than in healthy controls. Further, the cause-specific and relapse-free survival rates were lower among HNSCC patients with high MMP-9 and TIMP-1 serum levels compared to patients with low levels of circulating MMP-9 and TIMP-1. A significant correlation was shown between circulating MMP-9 and MMP-9 immunohistochemical staining in the corresponding tumors. No correlation was found between tissue or circulating levels of gelatinases or their inhibitors and the traditional clinical or histopathological factors, except for the association between tissue and circulating TIMP-1 and the size of the primary tumor.
Taken together, these results suggest that tissue expression of gelatinases and their inhibitors as well as pretreatment circulating MMP-9 and TIMP-1 levels could be prognostic in estimation of the clinical course of HNSCC. The results indicate further studies are needed with larger patient materials.
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Humanos, Profesores del curso Recursos. "Recursos humanos: unidad 9, material del alumno 2007-2." Universidad Peruana de Ciencias Aplicadas - UPC, 2007. http://hdl.handle.net/10757/272579.
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Ortiz, Elías José Agustín. "Individuo, grupo y empresa: clase 9, presentación 2007-2." Universidad Peruana de Ciencias Aplicadas - UPC, 2007. http://hdl.handle.net/10757/272672.
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Coughlan, Andrew Richard. "Matrix metalloproteinase (MMP) 2 and 9 in canine arthritis." Thesis, University of Liverpool, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243201.
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FONSECA, JACKSON WILLIAN MARQUES DA. "THE EXALTATION OF JESUS IN PHIL 2:9-11." PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO, 2016. http://www.maxwell.vrac.puc-rio.br/Busca_etds.php?strSecao=resultado&nrSeq=33787@1.
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PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIROCOORDENAÇÃO DE APERFEIÇOAMENTO DO PESSOAL DE ENSINO SUPERIOR
PROGRAMA DE SUPORTE À PÓS-GRADUAÇÃO DE INSTS. DE ENSINO
Filipenses 2,6-11 é texto fundamental na cristologia do cristianismo primitivo e neotestamentária. Inserido na parênese da carta de Paulo aos Filipenses, a passagem desenvolve uma narrativa cristológica que começa na preexistência, passa pela encarnação e culmina na exaltação de Jesus. No contexto da carta funciona como um chamado ético aos que estão em Cristo à obediência ao Senhor exaltado. Literariamente o texto é um hino composto de duas partes: 2,6-8 e 2,9-11, e a leitura proposta é ver nesta segunda seção o clímax do hino, que justamente trata da exaltação de Jesus. O tema da exaltação é apresentado dentro de uma perspectiva escatológica, pois o início do senhorio de Jesus é o cumprimento da esperança israelita no triunfo de Deus, é a virada escatológica que traz o tempo de salvação. Através da exaltação Deus compartilhou com seu Filho a soberania sobre o universo, implicando que todos os seres precisam agora dobrar os joelhos diante de Jesus e reconhecê-lo como Senhor. Aqueles que já fazem isso voluntariamente vivenciam antecipadamente o que será a realidade escatológica final. Esse novo papel de Jesus é descrito pelo título kurios, que combinado com outros elementos do texto atribui a ele contornos divinos e de igualdade com YHWH, além de uma oposição às ideologias romanas. A exaltação de Jesus também está ligada com a revolução cristológica que aconteceu no culto cristão primitivo, quando os cristãos judeus adoraram Jesus ao lado de Deus Pai, sem renunciar ao seu monoteísmo. O final do hino enfatiza exatamente que a exaltação de Jesus foi conduzida por Deus e resulta em sua própria glória.
Philippians 2,6-11 is a fundamental text in the Christology of early Christianity and the New Testament. Inserted in the parenesis of Paul s letter to the Philippians, the passage develops a Christological narrative that begins in the preexistence, passes through the incarnation and culminates in the exaltation of Jesus. In the context of the letter functions as an ethical call to those who are in Christ in obedience to the exalted Lord. Literarily, the text is a hymn composed of two parts: 2,6-8 and 2,9-11; and the proposed reading is to see in this second section the climax of the hymn, which precisely deals with the exaltation of Jesus. The theme of exaltation is displayed within an eschatological perspective, since the beginning of the lordship of Jesus is the fulfillment of the Israelite hope in the triumph of God, it is the eschatological turn that brings the fulfillment of salvation. Through exaltation, God shared with His Son the sovereignty over the universe, implying that all beings must now bend to his knees before Jesus and acknowledge him as Lord. Those who already do so voluntarily experience in advance what will be the reality of the eschatological end. This new role of Jesus is described by the title kurios, which combined with the other elements of the text gives it contours to the divine and equality with YHWH, in addition to opposition to Roman ideologies. The exaltation of Jesus is also connected to the Christological revolution that happened in the worship of the early Christian, when the Jewish Christians worshipped Jesus alongside God the Father, without giving up their monotheism. The end of the hymn emphasizes exactly that the exaltation of Jesus was led by God and results in his own glory.
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JINGMARK, JOHANNA, and CHRISTIAN LOJEK. "IFRS 9 FAS 2 : EN UNDERSÖKNING AV INTRESSENTERNAS ATTITYDER." Thesis, Högskolan i Borås, Institutionen Handels- och IT-högskolan, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:hb:diva-20755.
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Bakgrund och problem: IASB beslutade 2008 att ersätta IAS 39 med IFRS 9 då IAS 39 ses som alltför omfattande och komplex. Processen har delats upp i tre faser. Fas 1 behandlar klassificering och värdering, fas 2 behandlar nedskrivningar och fas 3 behandlar säkringsredovisning. Denna uppsats behandlar endast fas 2. Både redovisare, revisorer och användare av finansiella rapporter anser standarden för finansiella instrument vara komplex. En orsak till komplexiteten är att finansiella instrument i sig är komplexa och begreppet finansiella instrument innefattar en vid variation av instrument. Det konstaterades även under den globala finansiella krisen att IAS 39 innehöll betydande brister.Syfte: Syftet med denna uppsats är att studera delar av arbetet IASB har gjort för att ersätta IAS 39 med IFRS 9, vilket ger oss möjlighet att studera fas 2 i detta examensarbete. Syftet är att se vad intressenter förväntar sig i redovisning av finansiella instrument och vad det finns för attityder angående förslaget till IFRS 9 fas 2.Avgränsningar: Eftersom det krävs att EU antar standarden för att den ska börja gälla i Sverige har vi även avgränsat oss till att titta på remissvar från enbart EU-länder.Metod: Studien har utförts med en kvalitativ metod där den empiriska undersökningen bestått av 22 remissvar som finns att tillgå på IASB:s hemsida.Resultat och slutsatser: Den genomförda undersökningen visar att det finns ett flertal olika åsikter angående IASB:s arbete med Exposure Draft. Många organisationer är överens om att man vill ha en mer principbaserad standard men vill samtidigt ha mer exempel att tillgå vilket återigen drar mot en mer regelbaserad standard. Slutsatsen är att Exposure Draft fortfarande ses som komplex dock inte i samma bemärkelse som IAS 39. Hur IASB löser denna problematik blir intressant att följa.Program: Civilekonomprogrammet
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Appalachia, East Tennessee State University Archives of. "Archives of Appalachia Newsletter (vol. 9, no. 2, 1988)." Digital Commons @ East Tennessee State University, 1988. https://dc.etsu.edu/archives-newsletter/32.
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Andersson, Anna-Lotta, and Emelie Andersson. "Att neka rivningslov enligt PBL 9 kap. 34 § 2." Thesis, Högskolan Väst, Avdelningen för Matematik, Data- och Lantmäteriteknik, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:hv:diva-15793.
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För att skydda kulturhistoriskt värdefulla byggnader från rivning används PBL 9 kap. 34 § 2 om byggnaden är placerad inom detaljplan eller områdesbestämmelser. Förarbeten till paragrafen är tydliga med att vad som definieras som kulturhistoriskt ska avgöras med hänsyn till lokala överväganden. När en ansökan om rivningslov inkommer till kommunen ska den prövas mot PBL 9 kap. 34 § 2. För att kunna neka rivning ska byggnaden uppfylla rekvisitet kulturhistoriskt värdefull. Det kulturhistoriskt värdefulla kan vara byggnaden i sig eller den helhetsmiljö byggnaden är en del utav. För att styrka det kulturhistoriska värdet används utlåtanden från muséer, kulturinventeringar, privata företag med bebyggelseantikvarisk kompetens och kommunens egna planer. Kommunernas kulturhistoriska planer och program är inte alltid uppdaterade, vilket ställer högre krav på kunskapen om kulturhistoriskt värdefulla byggnader hos kommunernas tjänstepersoner. Studien tyder på att det finns en varierande kunskapsnivå bland tjänstepersonerna som deltagit i enkätundersökningen, i vissa fall förekommer feltolkningar av lagen. Det går inte att härleda kunskapsnivån till varken utbildning eller erfarenhet inom yrket. När tjänstepersonerna brister i kunskapen försvårar det kommunernas förutsättningar att följa lagens intentioner. För bedömning av en byggnads kulturhistoriska värde är bebyggelseantikvarisk kompetens till stor hjälp. Kommunerna bör uppdatera och utöka inventeringen av kulturhistoriskt värdefulla byggnader för att kunna göra kvalificerade avvägningar när det gäller att neka eller bevilja rivningslov. Studien visar på brister när det gäller kommunens information till fastighetsägare om fastighetsägarens rättighet till ersättning vid nekat rivningslov. Det är dessutom ovanligt att kommunerna budgeterar för denna ersättning. Det är svårt att avgöra varför kommunerna brister i informationen till fastighetsägarna och om bristen av budget leder till sämre information. Faktum kvarstår dock, kommunen är skyldig att ersätta fastighetsägaren om skadan av det nekade rivningslovet uppfyller kvalifikationsgränsen betydande skada i förhållande till värdet på berörd del av fastigheten. Lagstiftningen är tydlig, men kunskapen behöver spridas bland Sveriges kommuner för att i större utsträckning möjliggöra bevarandet av kulturhistorsikt värdefulla byggnader.To protect culturally valuable buildings from demolition Planning and Building Act chapter 9 section 34 p. 2 is used if the building is located within the detailed development plan or area regulations. Preparatory work on the section is clear that what is defined as cultural history must be decided regarding local considerations. When an application for demolition permit is submitted to the municipality, it must be tested against Planning and Building Act chapter 9 section 34 p. 2. To deny demolition, the building must meet the cultural heritage prerequisite. The cultural-historical value may be the building itself or the overall environment the building is part of. To prove the cultural-historical value, statements from museums, cultural inventories, private companies with building antiquarian competence and the municipality's own plans are used. The municipalities' cultural history plans and programs are not always updated, which places higher demand on the knowledge of culturally valuable buildings in the municipal's officials. The study indicates that there is a varying level of knowledge among the officials who participated in the survey, in some cases there are misinterpretations of the law. It is not possible to deduce the level of knowledge neither to education nor experience in the profession. When the officials knowledge is not sufficient municipalities make desitions in conflict with the intentions of the law. The competence of conservation officers is of good help for the building committee in assessing the cultural historical value of a buildning. Municipalities should update and expand the inventory of culturally valuable buildings to be able to make qualified assesments when it comes to denying or granting demolition permits. This study shows deficiencies in the municipality's information to property owners about their rights to compensation in the event of a denied demolition permit. Furthermore, it is unusual for municipalities to budget for this compensation. It is difficult to determine why the municipality's lack in information to property owners and whether the lack of budget leads to deficient information. However, the fact remains, the municipality is obliged to compensate the property owner if the damage of the refused demolition permit meets the qualification, significant damage in relation to the value of the affected part of the property. The legislation is clear, but the knowledge needs to be spread among Sweden's municipalities in order to enable the preservation of culturally valuable buildings.
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Wilson, Stephen G. "1 Peter 2:9 Christian witness in the world /." Theological Research Exchange Network (TREN), 1994. http://www.tren.com.
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Tanamachi, Amanda Rodrigues A. R. "Potencial toxicogenômico do contaminante ambiental 2-fenilbenzotriazol-9 não clorado (non-Cl PBTA-9) in vivo." Botucatu, 2020. http://hdl.handle.net/11449/192455.
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Orientador: Daisy Maria Fávero SalvadoriResumo: O setor industrial, em constante expansão, gera, diariamente, resíduos com elevado potencial tóxico ao ambiente. Nesse contexto, a indústria têxtil apresenta grande impacto poluidor para a hidrosfera, devido aos compostos e processos químicos utilizados na coloração de tecidos. A literatura mostra que não há eficiência na remoção desses compostos, tanto por parte das fábricas, como em Estações de Tratamento de Água (ETAs) para o abastecimento humano. Pelo contrário, o processo de descontaminação pode tornar corantes do grupo azo, por exemplo, ainda mais tóxicos. Portanto, a poluição ambiental por essa classe de corantes vem sendo alvo de inúmeros estudos para a caracterização química e toxicológica, sobretudo dos subprodutos e intermediários gerados, dentre os quais os 2-fenilbenzotraizóis não clorados (non-Cl PBTA). Dentre eles, o non-Cl PBTA-9 tem recebido especial atenção por ser derivado do corante Disperse Violet 93, que tem sido detectado em maior quantidade nos corpos fluviais sob influência de atividades têxteis. Com base nesse cenário, o presente estudo objetivou investigar o potencial toxicogenômico do non-Cl PBTA-9 em camundongos. Foram testadas três concentrações do composto, 5, 50 e 500 μg/kg p.c., administradas aos animais por via gástrica (gavage) em dose única. Foram analisadas as frequências de micronúcleo em células de medula óssea, o nível de danos primários no DNA em células do sangue, fígado e cólon, além do padrão de expressão dos genes TP53, CYP1A1, NAT... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The constantly expanding industrial sector has been generating residues with high toxic potential to the environment. The textile industry has a heavily impact, polluting the hydrosphere due to chemical processes used. Literature shows that even after effluent treatment, toxic compounds are still present in the wastewater and in rivers. Moreover, the water decontamination can make some dyes compounds even more toxics. Currently, environmental pollution caused by azo dyes, their byproducts and intermediates, has been widely investigated. In this sense, the non-chlorinated 2-phenilbenzotriazole 9 (non-Cl PBTA 9) has received attention because it is derived from the dye Disperse Violet 93, which is detected in high quantity in surface waters under influence of textile activities. Thus, the aim of this study was to investigate the toxicogenomic potential of acute exposure to the non-chlorinated PBTA-9 in mice. The three doses tested (5, 50 and 500 μg/kg body weight) of the compound were orally (gavage) administered to the animals. Micronucleus frequency in bone marrow cells, primary DNA damage in blood, liver and colon cells, and gene (TP53, CYP1A1, NAT2 and CDKN1A) expression profiling in liver cells were analyzed. The results showed that the non-Cl PBTA 9 was genotoxic in blood and liver cells at the highest dose (500 μg/kg b.w.) and at doses of 5, 50 and 500 μg/kg b.w. in colon cells. Mutagenic effect in bone marrow cells was observed at 5 and 50 μg/kg b.w.. No histological al... (Complete abstract click electronic access below)
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Porter, Virgil. "A comparative study of Elijah and Elisha in light of 2 Kings 2:9." Theological Research Exchange Network (TREN), 1994. http://www.tren.com.
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Bergman, Robert Loring. "Matrix Metalloproteinases 2 and 9 in Normal Canine Cerebrospinal Fluid." Thesis, Virginia Tech, 2001. http://hdl.handle.net/10919/33750.
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Cerebrospinal fluid (CSF) analysis is a standard part of a diagnostic evaluation. Commonly evaluated components include the cell count, protein concentration, glucose, and cytology. CSF analysis can be diagnostic in some diseases such as fungal infections and CNS lymphoma. Often, CSF analysis is not specific, but more information can be obtained. Matrix Metalloproteinases (MMPs) are enzymes that have been found in human CSF. They are calcium and zinc dependent endoproteinases with overlapping substrates. They hydrolyze at least one component of tissue extracellular matrix (ECM), such as collagen or elastin. They are important in normal physiologic processes such as angiogenesis, reproduction and wound healing. One class of MMPs, the gelatinases, degrade gelatins and type IV collagen include MMP 2 and MMP 9. MMPs are important in many pathological processes that involve unregulated matrix destruction such as arthritis, neoplasia and CNS diseases. MMP2 is known to be constituitively produced in CSF while MMP 9 is present only in certain pathologic conditions such as multiple sclerosis, neoplasia and inflammatory diseases. We hypothesize that MMP2 is present in normal canine CSF while MMP 9 is absent.
Cerebrospinal fluid samples were taken from 23 normal dogs that were being used for other research purposes. Each CSF sample was evaluated immediately for red blood cells (RBCs), white blood cells (WBCs), protein, and glucose, and then stored at -70°C. Cytological examination was also performed. CSF samples were considered normal if the protein was less than 25 mg/dl, WBCs were less than 6 µl, and RBCs were less than 25 µl. Each dog was euthanized and the brains processed for routine histopathology. MMP analysis was done using gelatin zymography and an enzyme linked immunosorbent assay (ELISA). Bands of enzyme activity were visible following staining due to enzyme degradation of the gelatin. A commercially available polyclonal sandwich ELISA was used to identify the pro form of MMP2.
The mean WBC count for the CSF samples was 0.96 WBC/ml with a range of 0-3 WBC/ml. The mean protein was 12 mg/dl, with a range of 8-17 mg/dl. The mean RBC count was 3.65 RBC/ml with a range of 0-21 RBC/ml. All normal samples of CSF contained a band of clearing that corresponded to the human commercial standard of proMMP2. No other major bands of clearing were noted on normal samples. The commercial human standards also contained ProMMP2. Other bands were present, but were faint and variable. Using a polyclonal antibody based sandwich ELISA, with samples run in triplicate, the mean pro MMP 2 levels were determined to be 5.61 ng/ml with a range of 3.36 - 10.83 ng/ml.
We conclude that normal CSF values are narrower than what has been previously reported for protein concentration and WBC count. Also, the pro form of MMP 2 is present in normal canine CSF based on results of gelatin zymography and ELISA.Master of Science
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Wagner, J. Ross. "The use of Psalm 8 in Hebrews 2:5-9." Theological Research Exchange Network (TREN), 1994. http://www.tren.com.
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Center, University of Arizona Water Resources Research. "Arizona Water Resource Vol. 9 No. 2 (September-October 2000)." Water Resources Research Center, College of Agriculture, University of Arizona (Tucson, AZ), 2000. http://hdl.handle.net/10150/316526.
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The U.S. Department of Energy recently announced a new initiative "GeoPowering the West," an effort to promote the development and use of geothermal power in the western states. According to DOE, all of Arizona's neighboring states have good geothermal resources, with California, Nevada and Utah listed as the top three states with electrical generation potential and New Mexico considered a high potential state. Arizona does not make the rankings.
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Sun, Jian-Sheng. "Etats excites et relaxation de la 2-methoxy,6-chloro,9-aminoacridine : interactions d'oligonucleotides lies a la 2-methoxy,6-chloro,9-aminoacridine et d'acides nucleiques." Paris 6, 1987. http://www.theses.fr/1987PA066634.
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Sun, Jian-Sheng. "Etats excités et relaxation de la 2-méthoxy, 6-chloro, 9-aminoacridine interactions d'oligonucléotides liés à la 2-méthoxy, 6-chloro, 9-aminoacridine et d'acides nucléiques /." Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb37610052t.
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Rauvala, M. (Marita). "Matrix metalloproteinases -2 and -9 and tissue inhibitors of metalloproteinases -1 and -2 in gynaecological cancers." Doctoral thesis, University of Oulu, 2006. http://urn.fi/urn:isbn:951428187X.
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Abstract
The invasion of a tumour through tissue limiting basement membranes is the critical step in malignant growth. Gelatinases (MMP-2 and MMP-9) are endopeptidases capable of degrading extracellular and pericellular matrix proteins such as collagen IV, the major component of basement membranes. An over-expression of these gelatinases is generally found in malignant tumours and is linked to impaired prognosis in many cancer types. Tissue inhibitors of metalloproteinases (TIMPs), endogenous regulators of the MMP activity, have recently been introduced as multifunctional proteins, which have paradoxical roles in tumour growth. Little data exists on the clinical significance of the gelatinases and TIMPs in gynaecological cancers.
In this study the clinical significance of the gelatinases was studied in endometrial and uterine cervical cancers by using immunohistochemical staining with specific antibodies. In epithelial ovarian cancer (EOC) these enzymes and their TIMPs were studied in the preoperative serum samples using ELISA assay. Additionally, sequential serum measurements were performed during chemotherapy to evaluate them as treatment response indicators.
In endometrial cancer, MMP-9 positivity correlated to a poor histological differentiation and an advanced clinical stage. High MMP-2 expression correlated to a poor differentiation, and unfavourable survival in stage I cancers, with mortality rates of 5% and 19% in patients with MMP-2 negative versus intensively MMP-2 positive tumours, respectively. In cervical cancers high MMP-2 expression correlated to an increased mortality risk. High MMP-9 expression was connected to a good differentiation of a tumour.
In EOC, a high circulating TIMP-1 value correlated to all the examined aggressive features of EOC, including poor survival. The serum measurements of TIMP-1 were uninformative about response evaluation during chemotherapy but paradoxically, an increase in gelatinases and TIMP-2 seemed to reflect a good response to treatment.
In conclusion, the data from this study show that high MMP-2 expression in tumour tissue could be prognostic in endometrial and cervical cancer, and preoperative circulating TIMP-1 could serve as an additional prognostic marker in EOC. Studies with larger patient cohorts would be necessary to further explore the value of these enzymes in clinical practice in gynaecological cancers.
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), Arbeitskreis Militär und Gesellschaft in der Frühen Neuzeit e. V. (Hrsg. "Militär und Gesellschaft in der Frühen Neuzeit [9 (2005) Heft 2]." Universität Potsdam, 2005. http://opus.kobv.de/ubp/volltexte/2006/673/.
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Aus dem Inhalt dieser Ausgabe:BEITRÄGE:
Matthew Glozier: William of Orange and the reception of Huguenot Soldiers in the Netherlands and Great Britain 1685–1688, Stefan Kroll: Die Autobiographie des kursächsischen Fouriers Friedrich Christian Sohr (1748 bis 1788): Einführung zu einer kritischen Edition im Internet,
PROJEKTE: Griet Vermeesch: War, fortified towns and the countryside, Gorinchem and Doesburg (1570-1680,
BERICHTE:
Michael Hochedlinger: „Der schlafende Riese“ : Das Österreichische Staatsarchiv, Abteilung Kriegsarchiv, Ulrike Kleemeier: „Clausewitz in the 21st Century“ (Oxford, 21. bis 23. März 2005), Daniel Krebs: "War in an age of revolution : the wars of American independence and the French revolution, 1775 – 1815" (10. bis 12. März 2005 am Deutschen Historischen Institut, Washington D.C.),
REZENSIONEN:
Thomas Fuchs: Peter Broucek und Kurt Peball, Geschichte der österreichischen Militärhistoriographie, Köln u. a. 2000, Heinrich Lang: Bernd Roeck und Andreas Tönnesmann, Die Nase Italiens. Federico da Montefeltro, Herzog von Urbino, Berlin 2005, Heinrich Lang: Maurizio Arfaioli: The black bands of Giovanni : infantry and diplomacy during the Italian wars (1526-1528). Pisa, 2005, Olaf Jessen: Martin Winter, Untertanengeist durch Militärpflicht? : das preußische Kantonsystem in brandenburgischen Städten im 18. Jahrhundert, Bielefeld 2005, Daniela Feistauer: Thomas Josef Mitterecker, Das Erzstift Salzburg im Zweiten Koalitionskrieg : Kämpfe - Besetzung - Folgen, Frankfurt/Main 2001,
ANKÜNDIGUNGEN:
Graduiertenworkshop 28. Januar 2006, „Institutionelle Ordnungen, Schrift und Symbole“, Europäisches Graduiertenkolleg 625 „Institutionelle Ordnungen, Schrift und Symbole“, Forschungskolloquium: Neuere Forschungen zur Militärgeschichte, Universität Potsdam, Wintersemester 2005/6215
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Schmidt, Maximilian. "AAV-2/9 vermittelter Gentransfer in porcine Kardiomyozyten im heterotopen Herztransplantationsmodell." Diss., lmu, 2012. http://nbn-resolving.de/urn:nbn:de:bvb:19-152012.
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Ferreira, Monica (editor), Valerie Moller, and HSRC/UCT Centre for Gerontology. "Southern African Journal of Gerontology, volume 9, number 2, October 2000." HSRC/UCT Centre for Gerontology, University of Cape Town, 2000. http://hdl.handle.net/10962/d1012915.
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[From Editorial] In this special issue of SAJG, an attempt is made to demonstrate how a selection of studies were conducted and how the research outcomes have been translated into action. Heslop, Agyarko, Adjetey-Sorsey and Mapetla give us a paper in which they have evaluated the methodology used in studies in Ghana and South Africa to determine the contributions of older people. After long periods of implementation and learning, this participatory-research methodology has become synonymous with HAl's research work. The authors take us through the methodology, describe the studies carried out in the two countries, and provide us with a vivid picture of not only the problems which older people in the countries face, but also the immense contribution which they make to the well-being of other people. The impact which this work has had in both countries is notable. Older participants in the studies have taken it upon themselves to advocate their rights, and the governments in the two countries have started to put measures in place to address some of the problems identified in the studies. The paper by Van Vuuren and Groenewald examines the pattern of expenditure of pension income by black pension beneficiaries in the Free State Province of South Africa, against a backdrop of these persons' living circumstances. It goes into detail about issues regarding the payment of pensions, pension sharing within households and expenditure of pension money on specific items, and challenges allegations that pensioners are frequently robbed of their pension money and that they lose this income to loan sharks. Some of the findings of this paper contrast with the findings of the HAl studies conducted with partners in the Northem, Gauteng and Kwazulu-Natal provinces of South Africa (see the first paper in this issue by Heslop and colleagues). In their paper, Kowal, Wolfson and Dowd point out that there is a dearth of empirical and credible data on older people in Africa. Although some research has been conducted on this population, the authors note that by and large the available data derive from small samples, are scattered, and have neither been widely disseminated nor shared. The authors further note a lack of common approaches to data collection. Realising these gaps, the World Health Organisation arranged a workshop in Harare, Zimbabwe in January 2000, to begin a process to develop a minimum data set (MDS) for use by researchers in Africa. An overall aim of the MDS project is to provide data to influence policy and decision makers in various areas which affect older persons.Needs-driven research on nutrition and ageing, carried out by HAl in collaboration with the London School of Hygiene and Tropical Medicine, is reported by Busolo, Ismail and Peachey in their paper. Nutrition and ageing in developing countries is an area which bas received scant attention. The nutritional requirements of older persons in these countries have not only been inadequately investigated but as a result, nutrition practitioners in various settings simply shoot in the dark. The authors take us down the path which the research took, from bow the needs were identified, to how the research was conducted, to how an intervention programme was set up. They give us some key findings of the research, describe the dissemination process and the application of the findings, and suggest a way forward. An Africa-wide programme currently being implemented as a direct result of this work is aimed at providing knowledge and information on the nutritional requirements of older people to key nutrition institutes, older people's organisations, N GOs (particularly those working in emergency situations), donors and governments. HelpAge International earlier conducted research in the Magu district of Tanzania on the plight of older women who are victimised on suspicion of their being witches (cf. Forrester Kibuga, 1999). Forrester Kibuga and Dianga now draw on this work in their paper. The authors take us through facts pertaining to the witchcraft-related killings, some of the problems which older people in the district face, the changing roles of older people in that area, beliefs and customs of the communities, and the stance of the government and the church on witchcraft. The dynamics of gender issues are also discussed. Following on this research, HAl designed and is now implementing a programme aimed at addressing some of the factors which lead up to these killings and developing sustainable structures to protect older people from violence. In his paper, Gorman draws on the work of HAl in various parts of the world, particularly in Africa - including Tanzania, Ghana, South Africa and Kenya. He argues that violence against older women and men in Africa cannot be attributed to a single, straight-forward problem but must be understood within a complex web that touches on history, family structures, and social and economic factors. He makes practical suggestions on what needs to be done to deal with the problem of violence. HelpAge International will soon be implementing an Africa-wide programme as a response to some of the issues which have been raised in its research on violence. While there is a clear need for more research on ageing in Africa, the research should not be done in a vacuum. There is a simultaneous need for greater collaboration and sharing of research results, and perhaps most importantly, for more action based on research outcomes. At the end of the day researchers should never forget that they have an ethical commitment to their subjects, to society and to their colleagues.
Thanks are due to Karen Peachey and Alex Dianga in the HAl Africa Regional Development Centre for the co-ordination of this special issue. Special thanks are due to Monica Ferreira for dedicating the issue to the experience and work of HAl, and for her commitment to addressing issues pertaining to ageing in Africa. She has worked tirelessly to ensure the success of not only this issue of SAJG but of previous issues as well. I have found her a pillar of support and a pleasure to work with. Tavengwa M. Nhongo.
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Mendonça, Thais Accorsi. "Avaliação de metaloproteinases de matriz -2, -9 e timp-2 em polpas dentais humanas sadias e inflamadas." [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/289923.
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Orientadores: Alexandre Augusto Zaia, Sergio Roberto Peres LineTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
Made available in DSpace on 2018-08-13T01:17:07Z (GMT). No. of bitstreams: 1 Mendonca_ThaisAccorsi_D.pdf: 1140557 bytes, checksum: edc0e3c618eed2eddfe927042cc99ba1 (MD5) Previous issue date: 2009
Resumo: As metaloproteinases de matriz (MMPs) são enzimas zinco dependentes secretadas por diversas células e que possuem uma importante função no remodelamento da matriz extracelular tanto em processos fisiológicos quanto patológicos. Essas enzimas são secretadas na forma inativa (zimógeno) e sua atividade pode ser modulada por inibidores teciduais endógenos (TIMPs). As MMPs são subdivididas de acordo com seu substrato, sendo as MMPs -2 e -9 conhecidas como gelatinases por degradar gelatina, ou seja, colágeno denaturado. Em uma inflamação pulpar intensa ocorre degradação tecidual similar à qualquer outro processo inflamatório. Dessa forma, o objetivo deste estudo foi avaliar polpas dentais humanas sadias e inflamadas quanto à expressão gênica de MMP-2, MMP-9 e TIMP-2 utilizando o PCR em tempo real; valores proteicos de TIMP-2 através do ELISA e atividade gelatinolítica de MMP-2 e MMP-9 por meio da técnica zimográfica. A técnica de quantificação de mieloperoxidase (MPO) também foi realizada em todas as amostras para identificar e quantificar a presença de células neutrofílicas na polpa. Foram utilizadas polpas sadias (n=20) de terceiros molares inclusos e polpas inflamadas (n=20), caracterizadas clinicamente. Os resultados mostraram uma expressão gênica 9 vezes maior para MMP-9 em polpas inflamadas quando comparadas a polpas sadias. Para a quantificação proteica, os valores absolutos evidenciaram maiores valores de TIMP-2 em polpas inflamadas quando comparadas com polpas sadias (p<0,0039). A atividade gelatinolítica para o grupo sadio evidenciou maior presença de bandas para pro-MMP-2, com ausência de MMP-9. Em polpas inflamadas, a proteína que apresentou maior atividade foi a MMP-9, com atividade significantemente maior (p=0,00081) quando comparada com MMP-2 ativa. O resultado da quantificação da proteina MPO evidenciou para algumas amostras inflamadas, caracterizadas clinicamente, um padrão similar ao encontrado para polpas sadias. E em amostras inflamadas com alto índice de MPO, caracterizando assim presença de muitos neutrófilos, houve presença de atividade gelatinolítica para MMP-9. Assim, pode-se concluir que a proteína MMP-2, em polpas inflamadas, tornou-se ativa mesmo com o aumento da produção de TIMP-2. Entretanto, o aumento em níveis proteicos para TIMP-2 na inflamação, não foi acompanhado do aumento do RNAm para este gene. Em processos inflamatórios, MMP-2 e MMP-9 foram encontradas de forma ativa, o que não ocorreu em polpas sadias. Não houve correlação entre sintomatologia e presença da proteína mieloperoxidase ou atividade gelatinolítica em polpas inflamadas
Abstract: Matrix Metalloproteinases (MMPs) are members of a family of zinc-dependent endopeptidases which are involved in the degradation of extracellular matrix but also in a number of other biologic processes. Such as any other inflammatory process, the pulp inflammation is associated with tissue degradation which can be mediated by MMPs. MMP-2 and MMP-9, named gelatinases, are secreted in latent form (zymogen) and their activity can be modulated by tissue inhibitors of metalloproteinases (TIMPs). The aim of this study was evaluated the role of MMP-2, MMP-9 and TIMP-2 in inflammatory human dental pulp tissues. Twenty dental pulp clinically diagnosed as inflammatory tissues and twenty healthy pulp tissues from enclosed third molars were harvested and evaluated to: gene expression of MMP-2, MMP-9 and TIMP-2 by real-time PCR; protein quantification of TIMP-2 by ELISA; gelatinolytic activity (MMP-2 and MMP-9) assessed by zymography technique, and neutrophils quantification by mieloperoxidase protein (MPO) assay. Data analysis showed an increased mRNA levels of MMP-9. Protein level of TIMP-2 in inflammatory pulp tissues was higher than healthy tissues (p<0,0039). The gelatinolytic activity for the healthy pulp tissues revealed a greater presence of bands for pro-MMP-2, with absence of MMP-9 bands. In inflammatory pulp tissues, MMP-9 demonstrated higher activity (p=0.00081) compared to MMP-2. Finally, the inflammatory pulp tissues with increased MPO protein levels were associated to the MMP-9 gelatinolityc activity. Taken together, these data suggest that MMP-2 in inflammatory pulp tissues was activated even at the presence of high levels of TIMP-2. However, the increased protein levels of TIMP-2 in inflammatory pulps were not followed by an increase of corresponding mRNA levels. During inflammatory process, MMP-2 and MMP-9 were found active, which did not occur in healthy pulps. Besides, it was not observed correlation between pain and the presence of mieloperoxidase protein or gelatinolytic activity in inflammatory pulp tissues
Doutorado
Endodontia
Doutor em Clínica Odontológica
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Honkavuori-Toivola, M. (Maria). "The prognostic role of matrix metalloproteinase-2 and -9 and their tissue inhibitor-1 and -2 in endometrial carcinoma." Doctoral thesis, Oulun yliopisto, 2014. http://urn.fi/urn:isbn:9789526204505.
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Abstract Endometrial carcinoma is the most common gynegologic malignancy in developed countries. Due to early symptoms, including abnormal uterine bleeding, endometrial cancer is often diagnosed at an early stage and in that case usually has a good prognosis and high cure rates. However, the nature of the disease is heterogeneous. During the last decades, the improvement in survival rates among endometrial cancer patients has not been significant, suggesting that the traditional clinicopathological factors may be inadequate to identify patients with high-risk disease. Furthermore, aggressive adjuvant treatments can be costly and very toxic. Therefore, better prognostic markers associated with biological aggressiveness of endometrial carcinoma are needed to identify the patients with high-risk disease, and to be able to select the treatment more individually. Gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) have been found to play a role in tumor progression. In the present work, the expression and prognostic value of MMP-2, MMP-9, TIMP-1 and TIMP-2 were assessed in endometrial carcinoma. The patient material consisted of a total of 266 women diagnosed with primary endometrial carcinoma. The tissue expression of immunoreactive proteins was examined in paraffin-embedded tumor sections by immunohistochemical staining using specific antibodies, and the pretreatment serum levels of the proteins were quantitatively measured by ELISA. Tissue MMP-2 expression associated with a worsened prognosis, whereas tissue TIMP-2 overexpression was an indicator of a favorable outcome. Furthermore, we observed a combination of strong MMP-2 and weak TIMP-2 tissue expression to identify a group of women at high risk of adverse outcome in endometrial carcinoma. Patients with negative MMP-2 immunostaining had the best prognosis, regardless of TIMP-2 staining result. In serum measurements, high preoperative TIMP-1 concentration was a prognostic indicator of unfavorable outcome. These results indicate that tissue MMP-2 and TIMP-2 as well as circulating TIMP-1 may be prognostic markers in endometrial carcinoma. Of these, tissue MMP-2 seems to be the most potent prognostic marker. Studies with larger patient materials are needed to further explore the value of these enzymes in clinical practice in endometrial cancerTiivistelmä Kohdunrungon syöpä on yleisin gynekologinen maligniteetti kehittyneissä maissa. Varhaisten oireiden, kuten poikkeavan verisen vuodon, vuoksi kohdunrungon syöpä havaitaan usein varhaisessa vaiheessa, jolloin sen ennuste on hyvä. Taudin käyttäytyminen voi kuitenkin olla moninaista. Viime vuosikymmenten aikana kohdunrungon syöpään sairastuneiden ennuste ei ole merkittävästi parantunut. Vaikuttaisi siltä, että perinteiset ennustetekijät eivät ole riittävän tarkkoja ennustamaan syövän taudinkulkua. Lisäksi liitännäishoidot voivat olla kalliita, ja niihin voi liittyä vakavia haittavaikutuksia. Uusien biologisten ennustetekijöiden löytäminen olisi tärkeää, jotta aggressiivista syöpätyyppiä sairastavat potilaat pystyttäisiin tunnistamaan entistä paremmin, ja hoito kyettäisiin räätälöimään yksilöllisemmin taudinkuvaa vastaavasti. Gelatinaasien (MMP-2 ja MMP-9) sekä niiden kudosinhibiittoreiden (TIMP-1 ja TIMP-2) on havaittu osallistuvan syövän etenemiseen. Tässä tutkimuksessa tarkasteltiin MMP-2:n ja MMP-9:n sekä niiden kudosinhibiittoreiden TIMP-1:n ja TIMP-2:n ilmentymistä ja ennusteellista merkitystä kohdunrungon syövässä. Aineisto käsitti yhteensä 266 primaariseen kohdunrungon syöpään sairastunutta naista. Määritysmenetelminä käytettiin sekä immunohistokemiallista värjäystä parafiiniin valettujen kudosnäytteiden osalta että ELISA-määrityksiä ennen hoitoa otettujen seeruminäytteiden osalta. Syöpäkudoksen runsas MMP-2 -proteiinin ilmentyminen liittyi epäsuotuisaan ennusteeseen, kun taas kasvainkudoksen voimakas TIMP-2 -proteiinin ilmentyminen oli hyvän ennusteen merkki. Lisäksi kasvainkudoksen voimakkaan MMP-2- ja heikon TIMP-2 -proteiinien ilmentymisen yhdistelmän havaittiin liittyvän suurempaan syövästä johtuvaan kuolleisuuteen. MMP-2 -negatiivisten potilaiden eloonjäämisennuste oli paras, TIMP-2 -värjäystuloksesta riippumatta. Seerumin korkea TIMP-1 -pitoisuus oli merkittävä huonontuneen ennusteen merkki. Tutkimuksen tulokset viittaavat siihen, että kasvainkudoksessa esiintyvät MMP-2- ja TIMP-2 -proteiinit samoin kuin seerumin TIMP-1 -pitoisuus voivat ennustaa kohdunrungon syövän kliinistä käyttäytymistä. Kasvainkudoksessa esiintyvä MMP-2 -proteiini vaikuttaisi olevan merkittävin ennusteellinen tekijä, mutta tulosten varmistamiseksi tarvitaan lisää tutkimuksia suuremmilla potilasaineistoilla
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Lucia, Conrado Ingraci de. "Análise quantitativa dos níveis de cálcio, Colagenase A e B durante o reparo ósseo em calvárias de ratos sob o modelo experimental de defeito ósseo." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/58/58137/tde-03042013-163708/.
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O osso é um tipo especializado de tecido com alto teor mineral e desempenha variadas funções no organismo, como a reserva de cálcio, proteção de estruturas vitais e alavanca para a movimentação dos musculos. Constantemente o osso passa por processos de remodelação, o que mantém sua estrutura funcional e repara pequenas fraturas que ocorrem normalmente devido ao estresse do uso contínuo. O sistema de reparo funciona em perfeita sincronia mediante células que produzem os componentes ésseos e células que os reabsorvem permitindo a organização do tecido. Esse sistema de manuteção depende da interação entre estas células bem como dos sinais enviados por mediadores e moduladores. Varias proteínas funcionam como indutores de formação óssea, mas também no sentido de facilitar essa reconstrução. Dentre estas proteínas se encontram as BMPs, que possuem grande potencial osteoindutor, e MMPs, que atuam em diversas fases da construção e manutenção deste tecido. Particularmente a BMP-2 tem mostrado um potencial significativo em termos de indução e sua forma recombinante a rhBMP-2, produzida por engenharia recombinante, foi liberada para comercialização e utilizacao clínica. Quanto às MMPs, há importante função das MMP-2 e MMP-9 neste tecido. A primeira estruturando a matriz e modulando o processo de reabsorção nos processos inflamatórios inerentes ao reparo; a segunda atuando desde fases iniciais às tardias, produzida principalmente por osteoclastos e utilizada na remodelação do osso novo. Porém, esta capacidade de reparo do osso é limitada e defeitos ósseos de grande extensão exigem muito do organismo, podendo levar a um reparo que não se estrutura devidamente. Assim, várias técnicas foram propostas para estimular o desenvolvimento ósseo e a utilizacao de enxertos se mostrou eficaz para fornecer um arcabouço de crescimento, facilitando a implantacao do osso neofomado e protegendo o leito do defeito durante todo o extenso período de recuperação. O presente estudo enfocou três diferentes tipos de enxerto ósseo (autólogo, homólogo e heterólogo) e suas associações com a proteína rhBMP-2, verificando sob o aspecto bioquímico a relação de cada um com a quantidade de MMP-2 e MMP-9 em dois tempos de reparo diferentes. De maneira geral, verificou-se que no primeiro momento há maior produção de MMP-2 e os níveis de MMP-9 se mantém de forma relativamente constante nos dois tempos cirúrgicos. O enxerto autólogo apresenta melhores resultados, seguido dos obtidos no enxerto homólogo e heterólogo respectivamente, entretanto a adição de rhBMP-2 a estes enxertos não parece influenciar nos níveis de MMP-2 e MMP-9 nos dois períodos. A dosagem de cálcio revelou que se apresentavam mais mineralizados os grupos de enxerto autólogo e homólogo, os demais grupos além de apresentar menores niveis de cálcio, ainda decresceram nestes níveis no segundo período do experimento.Bone is a special tissue with a high mineral content and performs various functions in the body, such as calcium reserves, protection of vital structures and muscles lever during the movement. Bone constantly undergoes remodeling processes, which keeps its functional structure and repair small fractures that commonly occur due to the stress of continuous use. The repair system works perfectly synchronized by the cells that produce bone components and resorbing cells, allowing the perfect tissue organization. This maintenance system depends on the interaction between these cells and the signals sent by mediators and modulators. Several proteins operate to induce bone formation, but also to facilitate the reconstruction. Among these proteins are the BMPs, which have great osteoinductive potential, and MMPs that act at different stages of construction and maintenance of this tissue. Particularly BMP-2 has shown significant potential in terms of induction and its recombinant form, rhBMP-2, produced by recombinant engineering, has been released for clinical use and commercialization. In relation to MMPs, there are important functions of MMP-2 and MMP-9 in this tissue. First, structuring the matrix and modulating the resorption during inflammatory processes inherent to repair; second, acting at early to later stages, produced mainly by osteoclasts and used during bone remodeling. However, this repair capacity is limited and large bone defects require a lot of strength of the body, may leading to a bone repair not well structured. Thus, several proposed techniques to stimulate the development and use of bone grafts were effective to provide a framework for growth, facilitating the implementation of new bone and protecting the defect bed throughout the extended recovery period. This study focused on three different types of bone graft (autologous, homologous and heterologous) and their association with rhBMP-2 protein, evaluating the biochemical aspects according to the amount of MMP-2 and MMP-9 in two different periods of time. In general, it was found that firstly, there is an increased production of MMP-2, and MMP-9 levels remain relatively constant in both considered periods of time. The autologous graft presented the best results followed by homologous and heterologous, respectively; however the addition of rhBMP-2 in these grafts did not seem to influence the MMP-2 and MMP-9 levels, in both periods of time. The calcium dosage revealed more mineralization at the autologous and homologous groups, the other groups, besides having lower calcium levels, decreased these levels at the second period of this experiment.
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Rask, Madeleine. "Fördelning av en medgäldenärs brist : Förhållandet mellan 2 § skuldebrevslagen och 9 § preskriptionslagen." Thesis, Internationella Handelshögskolan, Högskolan i Jönköping, IHH, Redovisning och Rättsvetenskap, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-15089.
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Clegg, Peter David. "Matrix metalloproteinase-2 and -9 and their inhibitors in equine joint disease." Thesis, University of Liverpool, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263792.
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Griffith, Gary Webster. "Abounding in generosity : a study of charis in 2 Corintheans 8-9." Thesis, Durham University, 2005. http://etheses.dur.ac.uk/1760/.
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Trajanovska, Emilija, and Josefin Sande. "Finansiella tillgångar : en komparativ studie av K3 och RFR 2/IFRS 9." Thesis, Högskolan i Borås, Akademin för textil, teknik och ekonomi, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:hb:diva-14381.
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I början av 2018 började den nya standarden IFRS 9, framtagen av IASB, gälla. Standarden ersätter den tidigare IAS 39 som behandlar finansiella instrument och är framtagen efter den stora finanskrisen under 2000-talet. I samband med implementeringen av IFRS 9 kan ett företags klassificerings, omklassificerings, redovisning och värdering samt nedskrivning av finansiella tillgångar påverkas annorlunda. Till följd av detta kommer det uppstå större skillnader mellan det svenska regelverket K3, som grundats på IFRS, och den nya standarden i IFRS beträffande finansiella tillgångar. Studien är en komparativ analys med typfall där tre fiktiva företag jämförs för att se vilka skillnader som finns mellan K3 och RFR 2/IFRS i hanteringen av finansiella tillgångar. De delar som belyses i studien är klassificering, omklassificering, redovisning och värdering samt nedskrivning. Skillnaderna som uppstår analyseras främst ur ett modifierat intressentperspektivmed inslag av positiv redovisningsteori och möjligheter till utdelning för investerare. Analysen i studien utgår till stor del från de kvalitativa egenskaperna som anges i IASB:s föreställningsram och i Bokföringsnämndens (BFN) vägledning för K3. De kvalitativa egenskaperna analyseras utifrån ett modifierat intressentperspektiv med investerare och företagsledare i fokus. Investerare har ett ekonomiskt intresse i företag och efterfrågarekonomisk information från företag som kan påverka deras prognoser och beslutstagande. Företagsledare använder den ekonomiska informationen för att kunna fatta viktiga beslut iföretaget. Det är även viktigt för företagsledaren att se om ett av regelverken har en större positiv effekt på redovisningen och därför är att föredra. Studiens syfte är att belysa de mest väsentliga skillnaderna angående finansiella tillgångar och deras förfarande och hur dessa skillnader påverkar investerare och företagsledare samtutdelningsmöjligheterna i ett företag. En redogörelse av de båda redovisningsstandarderna görs i början av studien för en lättare läsförståelse och för att ge läsaren en förståelse av de bådaregelverken. Analysen gällande de kvalitativa egenskaperna utifrån intressentteorin hjälper till att belysa de mest signifikanta skillnaderna mellan K3 och RFR 2/IFRS 9.Resultatet från studien visar att skillnaderna mellan regelverken främst är redovisningsteknisk i hur den finansiella informationen presenteras. Samtidigt som den största skillnaden mellanK3 och RFR 2/IFRS 9 gällande nedskrivningar inte har någon effekt på ekonomin i företaget på lång sikt. Slutsatserna från studien är att ett företag som väljer att tillämpa RFR 2/IFRS framför K3 kommer en del av de kvalitativa egenskaperna stärkas sett ur studiens intressentperspektiv. Väljer ett företag istället att tillämpa K3 kommer deras utdelningsmöjligheter upplevas starkare i ett tidigare skede på grund av periodiseringseffekterna. Vidare har studien praktiskt bidragit till att visa hur företag i praktiken kan tillämpa standarderna K3 och RFR 2/IFRS 9. Detta hjälper ett företag att välja vilken standard de ska välja när de står i ett vägval mellan vilken av standarderna de ska tillämpa.At the beginning of 2018, the new International Financial Reporting Standard (IFRS 9) developed by the International Accounting Standards Board (IASB), began to be valid. The standard replaces the previous International Accounting Standard (IAS) 39, which deals with financial instruments, and is developed after the major financial crisis during the 2000s. In correlation to the implementation of IFRS 9, a company's classification, reclassification, recognition and valuation and impairment of financial assets may be affected differently. As a result, there can be major differences between the Swedish regulatory framework K3, that is based on IFRS, and the new IFRS standard for financial assets. This study is a comparative analysis with hypothetical cases where three fictitious companies are compared to highlight the differences that exist between K3 and Rådet för finansiell rapportering (RFR) 2/IFRS in the management of financial assets. The parts that are brought up in the study are classification, reclassification, accounting and valuation as well as impairment. The differences that arise are mainly analyzed from a modified stakeholder perspective with elements of positive accounting theory and opportunities for dividend. The analysis in this study is largely based on the qualitative characteristics stated in the IASB Performance Framework and in the Accounting Board's guidance for K3. The qualitative characteristics are analyzed based on a stakeholder perspective with investors and business leaders in focus. Investors have a financial interest in companies and request financial information from companies that may affect their forecasts and decision making. Business executives use the financial information to make important decisions in the company. It is also important for the business manager to see if one of the standards has a positive effect on the accounting and is therefore preferable. The purpose of this study is to highlight the most significant differences regarding financial assets, their procedures and how these differences affect investors and business managers but also the dividend opportunities of a company. A presentation of the two regulations is made at the beginning of the study for an easier reading comprehension and to give the reader an understanding of the two accounting standards. The analysis of stakeholder theory helps to highlight the differences in K3 and RFR 2/IFRS 9 for the analysis of the qualitative characteristics of the report. The results in this study shows that the differences between the regulations are primarily accounting techniques in how the financial information is presented. At the same time the main difference between K3 and RFR 2/IFRS 9 regarding impairment does not affect the long-term economy of the company. The conclusions from the study shows that some of the companies qualitative characteristics will be strengthened if they choose to apply RFR 2/IFRS instead ofK3, seen from the perspective of the stakeholders in the study. If a company chooses to applyK3 instead, their dividend opportunities will be a lot bigger in an earlier stage due to the accrual effects. In addition, the study has practically contributed to demonstrate how companies effectively can apply the standards K3 and RFR 2/IFRS 9, that determine which of the standards will suit them best when choosing between them.
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ALMEIDA, Sinara Mônica Vitalino de. "Síntese, caracterização e aplicação biotecnológica do Dimetil-2-(Acridin-9-metileno) malonato." Universidade Federal de Pernambuco, 2011. https://repositorio.ufpe.br/handle/123456789/2257.
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Previous issue date: 2011Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
O presente trabalho teve por objetivo sintetizar e caracterizar parcialmente as propriedades luminescentes do derivado de acridina (LPSF/IP-81) e de seu conjugado com a lectina Concanavalina A (Con A). A síntese do LPSF/IP-81 foi realizada a partir de AC-2 e dimetilmalonato, por aquecimento à 110 °C por 24 h com rendimento de 33%. Avaliação por técnicas espectroscópicas das propriedades luminescentes do LPSF/IP-81 mostrou que o mesmo é fotoluminescente por meio de excitação em 360 nm, e emissão por volta de 428 nm. No entanto o LPSF/IP-81 mostrou-se fracamente quimiluminescente quando excitado a partir de reação química com peróxido de hidrogênio. O rendimento quântico luminescente foi de 2%. LPSF/IP-81 foi conjugado com a lectina Con A e o conjugado foi separado usando cromatografia de exclusão molecular com Sephadex G-25. O conjugado Con A-IP-81 foi avaliado por meio da atividade hemaglutinante, conteúdo protéico e luminescência (fluorescência ou quimiluminescência). Análise por dicroísmo circular mostrou manutenção da estrutura terciária da Con A após conjugação com LPSF/IP-81. Medidas de fluorescência do conjugado Con A-IP-81 demonstraram manutenção das propriedades luminescentes do LPSF/IP-81. Con A-IP-81 foi empregado como sonda histoquímica, onde o LPSF/IP-81 atuou como marcador luminescente, na avaliação do perfil sacarídico de superfície celular de tumores humanos de pele e mama. A marcação dos tecidos foi avaliada em luminômetro e microscópio de fluorescência. Os tumores de pele analisados ceratoacantoma (1,992 ± 177 RLU), ceratose actínica (2,127 ± 332 RLU), carcinoma epidermóide (2,920 ± 721 RLU) e carcinoma basocelular (2,934 ± 579 RLU) mostraram uma maior expressão de resíduos de α-D-glicose/manose reconhecidos pelo conjugado Con A-IP-81 comparado aos tecidos normais (579 ± 145 RLU). Da mesma forma que os tecidos de mama e pele analisados pela microscopia de fluorescência mostraram marcação positiva para o mesmo conjugado. Esses resultados indicam que o LPSF/IP- 81 pode ser usado como marcador em histoquímica
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Huppes, Rafael Ricardo [UNESP]. "Expressão gênica de MMP-2 e 9, TIMP-1 e 2, ATM, TP53, VEGF, COX-2 e CDH-1 no TVT canino." Universidade Estadual Paulista (UNESP), 2014. http://hdl.handle.net/11449/122030.
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000814346.pdf: 1337951 bytes, checksum: 9ed960afb83960e3296a726e4541f251 (MD5)A literatura cita que 1 a 5% dos casos de tumor venéreo transmissível (TVT) primário são metastáticos. Sendo assim, é importante estudar os mecanismos que colaborem para a invasão metastática assim como para sua implantação. Dentre estes mecanismos as metaloproteinases (MMP-2 e MMP-9) e seus inibidores (TIMP-1 e TIMP-2), assim como o ATM, COX-2, VEGF e CDH-1 podem explicar a implantação tumoral no sítio primário e a ocorrência da invasão metastática do TVT no cão. O objetivo do presente trabalho é avaliar a expressão gênica dos marcadores acima e correlacionar a sua expressão com o poder de implantação e invasão metastática no TVT. Para este estudo foram avaliadas 32 amostras tumorais, que foram congeladas e delas extraídos RNAm. Utilizou-se o método de qRT-PCR para todos os transcritos. Os resultados foram comparados com sangue periférico de 10 cães saudáveis (grupo controle) com o teste de Mann Whitney. A expressão gênica de MMP-2 e TIMP-1 foi significativamente maior do que o grupo controle (p < 0,001; p = 0,037; respetivamente). A expressão dos transcritos dos genes MMP-9 e TIMP-2 não apresentou diferença estatística entre o TVT e grupo controle (p = 0,535; p = 0, 906; respetivamente). A avaliação de expressão de transcritos do ATMapresentou aumento significativo (p < 0,0001) de sua expressão no tecido tumoral (TVT) quando comparado com o grupo controle, enquanto a expressão dos transcritos do gene TP53 não apresentou diferença estatística entre os grupos (p = 0,26). Na avaliação da COX-2, VEGF, CDH-1 foi verificado aumento significativo (p < 0,0001; p < 0,0001; p = 0,04, respectivamente) da expressão de transcritos dos genes no tecido tumoral (TVT) em relação ao grupo controle. A super-expressão de MMP-2 e o TIMP-1 pode explicar a capacidade de implantação das células tumorais assim como a maior expressão de VEGF e COX-2 pode explicar o crescimento rápido local do tumor e ...
The literature reports that 1-5% of cases of primary trasmissible venereal tumor (TVT) are metastatic. Thus, it is interesting to study the mechanisms that collaborate to the metastatic invasion and implantation of TVT. Among these mechanisms, the metalloproetinases (MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2), as well as ATM, COX-2, VEGF and CDH-1 may explain the tumoral implantation in the primary site and metastatic invasion of TVT in dogs. The objectives of this study are to evaluate the gene expression of these markers and to correlate their expression with the high ability of deployment and metastatic invasion of TVT. For this study, 32 tumor samples were frozen and their mRNA were extract using the qRT-PCR method for all transcripts. The results were compared with peripheral blood of 10 healthy dogs (control group) using the Mann Whitney test. The expression of MMP-2 and TIMP-1 were significantly higher than the control group (p <0.001, p = 0.037, respectively). The expression of MMP-9 and TIMP-2 showed no statistical difference between the TVT and the control group (p = 0.535, p = 0, 906, respectively). The expression of ATM was increased in tumor tissue (TVT) when compared with the control group, while the expression of TP53 had no statistical difference between groups (p = 0.26). The evaluation of COX-2, VEGF and CDH-1 were increas in tumor tissue when compared with control group. The over expression of MMP-2 and TIMP-1 may explain the implantation ability of the tumor cells, as well as the increase of VEGF and COX-2 may explain the rapid tumor growth and the rich vasculatization. While the over expression of ATM, TP53 and CDH-1 may contribute to the low metastatic capacity of the TVT tumor
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Huppes, Rafael Ricardo. "Expressão gênica de MMP-2 e 9, TIMP-1 e 2, ATM, TP53, VEGF, COX-2 e CDH-1 no TVT canino /." Jaboticabal, 2014. http://hdl.handle.net/11449/122030.
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Orientador: Renée Laufer AmorimCoorientador: Andrigo Barboza De Nardi
Coorientador: Mirela Tinucci Costa
Banca: Rosemere de Oliveira Vasconcelos
Banca: Geórgia Mode Magalhães
Banca: Rafael Torres Neto
Banca: Bruno Watanabe Minto
Resumo: A literatura cita que 1 a 5% dos casos de tumor venéreo transmissível (TVT) primário são metastáticos. Sendo assim, é importante estudar os mecanismos que colaborem para a invasão metastática assim como para sua implantação. Dentre estes mecanismos as metaloproteinases (MMP-2 e MMP-9) e seus inibidores (TIMP-1 e TIMP-2), assim como o ATM, COX-2, VEGF e CDH-1 podem explicar a implantação tumoral no sítio primário e a ocorrência da invasão metastática do TVT no cão. O objetivo do presente trabalho é avaliar a expressão gênica dos marcadores acima e correlacionar a sua expressão com o poder de implantação e invasão metastática no TVT. Para este estudo foram avaliadas 32 amostras tumorais, que foram congeladas e delas extraídos RNAm. Utilizou-se o método de qRT-PCR para todos os transcritos. Os resultados foram comparados com sangue periférico de 10 cães saudáveis (grupo controle) com o teste de Mann Whitney. A expressão gênica de MMP-2 e TIMP-1 foi significativamente maior do que o grupo controle (p < 0,001; p = 0,037; respetivamente). A expressão dos transcritos dos genes MMP-9 e TIMP-2 não apresentou diferença estatística entre o TVT e grupo controle (p = 0,535; p = 0, 906; respetivamente). A avaliação de expressão de transcritos do ATMapresentou aumento significativo (p < 0,0001) de sua expressão no tecido tumoral (TVT) quando comparado com o grupo controle, enquanto a expressão dos transcritos do gene TP53 não apresentou diferença estatística entre os grupos (p = 0,26). Na avaliação da COX-2, VEGF, CDH-1 foi verificado aumento significativo (p < 0,0001; p < 0,0001; p = 0,04, respectivamente) da expressão de transcritos dos genes no tecido tumoral (TVT) em relação ao grupo controle. A super-expressão de MMP-2 e o TIMP-1 pode explicar a capacidade de implantação das células tumorais assim como a maior expressão de VEGF e COX-2 pode explicar o crescimento rápido local do tumor e ...
Abstract: The literature reports that 1-5% of cases of primary trasmissible venereal tumor (TVT) are metastatic. Thus, it is interesting to study the mechanisms that collaborate to the metastatic invasion and implantation of TVT. Among these mechanisms, the metalloproetinases (MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2), as well as ATM, COX-2, VEGF and CDH-1 may explain the tumoral implantation in the primary site and metastatic invasion of TVT in dogs. The objectives of this study are to evaluate the gene expression of these markers and to correlate their expression with the high ability of deployment and metastatic invasion of TVT. For this study, 32 tumor samples were frozen and their mRNA were extract using the qRT-PCR method for all transcripts. The results were compared with peripheral blood of 10 healthy dogs (control group) using the Mann Whitney test. The expression of MMP-2 and TIMP-1 were significantly higher than the control group (p <0.001, p = 0.037, respectively). The expression of MMP-9 and TIMP-2 showed no statistical difference between the TVT and the control group (p = 0.535, p = 0, 906, respectively). The expression of ATM was increased in tumor tissue (TVT) when compared with the control group, while the expression of TP53 had no statistical difference between groups (p = 0.26). The evaluation of COX-2, VEGF and CDH-1 were increas in tumor tissue when compared with control group. The over expression of MMP-2 and TIMP-1 may explain the implantation ability of the tumor cells, as well as the increase of VEGF and COX-2 may explain the rapid tumor growth and the rich vasculatization. While the over expression of ATM, TP53 and CDH-1 may contribute to the low metastatic capacity of the TVT tumor
Doutor
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Vasala, K. (Kaija). "Matrix metalloproteinase MMP-2 and MMP-9 and their inhibitors TIMP-1 and TIMP-2 in bladder carcinoma." Doctoral thesis, University of Oulu, 2008. http://urn.fi/urn:isbn:9789514288746.
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Abstract
Bladder cancer when superficial has a good prognosis but it has a high recurrence risk and about 10–15% of the superficial carcinomas will progress into muscle invasive or metastatic type. The most powerful factor for predicting the behavior of bladder carcinoma is the stage of the tumor. Invasion to the lamina propria increases the risk of recurrence and progress to muscle-invasive tumor. Also grade of the tumor and tumor multiplicity associates with high risk for recurrence. New markers are still needed to find those patients who need more and better treatments to avoid the recurrence and progress. The need for new non-invasive markers to diminish the need for frequent cystoscopy in follow-up is also obvious.
Gelatinases MMP-2 and MMP-9 are known to associate to tumor invasion and progression. Also their tissue inhibitors TIMP-1 and TIMP-2 take part in these diversified processes and metastasis formation. In the present work the expression and clinical value of gelatinases MMP-2 and MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 were evaluated in bladder carcinoma. Primary tissue samples of 121 patients were analyzed for expression of MMP-2 and/or MMP-9 using immunohistochemistry. The serum samples of 87 patients who were treated in the Oncology Department of Oulu University Hospital were collected and studied with ELISA. The control group consisted of 44 healthy volunteers.
Overexperssion of MMP-2 protein correlated significantly to disease-specific survival and showed an independent prognostic value as a biomarker. High MMP-9 expression instead correlated to favorable overall survival of bladder cancer patients. Circulating proMMP-2, TIMP-2 and MMP-2:TIMP-2 complex levels were lower in cancer patients than in healthy volunteers in control group. High levels of all these three markers correlated with better prognosis in bladder cancer patients.
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Bednarek, Nathalie. "Mmp-2, -9, timp-1, -2 : recherche de biomarqueurs de lésions cérébrales chez l'enfant prématuré et à terme." Paris 7, 2008. http://www.theses.fr/2008PA077103.
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Les atteintes cérébrales périnatales sont une cause majeure de décès ou de handicap. TJôtre hypothèse est que les MMP-2 et -9 et les TIMP-1, -2 pourraient être des marqueurs précoces de ces lésions cérébrales. Le profil cortical des MMP-2, -9, TIMP-1 et -2 a été étudié de la vie embryonnaire à l'âge adulte. Les profils plasmatiques de nouveaux-nés ont été étudiés en fonction de l'âge gestationnel, du sexe et des pathologies rencontrées en période néonatale. Le profil des MMP-2, -9, TIMP-1 et -2 ont été étudiés au niveau du cortex et du plasma dans des modèles animaux. MMP-2, leTIMP-1 et le TIMP-2 sont très exprimés respectivement pendant la période embryonnaire et en post-natal. MMP-9 est peu exprimée quel que soit le temps étudié. Le sexe n'influence pas l'expression des MMP-2 et -9 et des TIMP-1 et -2 chez l'animal et chez l'homme. Les MMP-9 et TIMP-1 sont élevés spécifiquement en cas d'EAI dans le plasma humain mais aussi chez la souris. Chez le nouveau-né présentant des lésions de substance blanche, il n'est pas observé de modifications des concentrations des MMP-9 et TIMP-1 alors que, chez l'animal, TIMP-1 s'élève exclusivement, de façon transitoire, dans le cortex et le plasma. Cette étude préliminaire apporte des arguments justifiant des explorations complémentaires concernant la MMP-9 et le TIMP-1 en tant que marqueurs de sévérité et pronostic de l'EAIThe perinal brain injuries are a major cause of death or handicap. We hypothezise that the MMP-2, -9, and the TIMP- 1 and 2 could be early markers of these cerebral lesions. The cortical profile of MMP-2, -9, TIMP-1 and -2 was studied during embryonic life to adulthood. The plasmatic neonatal profiles were studied according to the gestational age, gender and neonatal pathologies. They were also studied in animal models of perinatal brain injuries. MMP-2, TIMP-1 are largely expressed during embryonic life and TIMP-2 more likely in early post-natal period. MMP-9 is quasi undetectable whatever the moment. Gender does not influence the expression of MMP-2, -9 and their inhibitors in the new-born as well as in the mouse. In ischemic encephalopathy, MMP-9 and TIMP- 1 are specifically raised in new-born plasma but also in mice brain and plasma. In PWMD new-born, no gelatinase or inhibitor elevation was seen, but in mouse cortex and plasma, an exclusive and transitory raise of TIMP-1 is obvious. This preliminary study brings arguments to explore MMP-9 and TIMP-1 as severity and prognosis markers in hypoxic-ischemic encephalopathy
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Peres, Regina Celia Rocha. "Analise dos polimorfismos na região promotora dos TGF 'Beta' -1, MMP-9, TIMP-2 e PAX-9 : correlação com a hipodontia." [s.n.], 2004. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288493.
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Orientador: Pedro Duarte NovaesTese (doutorado) - Universidade Estadual de Campinas. Faculdade de Odontologia de Piracicaba
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Resumo: Hipodontia, a ausência congênita de um ou mais dentes, é uma das alterações mais comuns da dentição humana. Os dentes mais atingidos são os terceiros molares, segundos pré-molares superiores, e incisivos laterais superiores. Embora hipodontia não represente um sério problema de saúde pública, pode causar disfunção na mastigação e fala, além de problemas estéticos. Os genes TGFBETA1, MMP9, TIMP2 e PAX9 estão expressos em várias regiões do germe dentário durante as diversas fases da odontogênese. Estudos recentes mostram que polimorfismos em regiões reguladoras da transcrição parecem ser freqüentes, e que estas variações são responsáveis por características fenotípicas individuais. No entanto, pouco se sabe sobre o papel de polimorfismos genéticos no surgimento da agenesia dental de forma isolada. O objetivo do presente estudo foi analisar a associação existente entre os polimorfismos na região promotora dos genes TGF BETA1, MMP9, TIMP2 e PAX9, e a agenesia dental de terceiros molares, segundos pré-molares e incisivos laterais. A amostra foi composta pelo DNA genômico de 50 indivíduos afetados e 50 indivíduos controles, com idade acima de 16 anos, para os três primeiros marcadores. Com o objetivo de aumentar a amostra, a análise de polimorfismos no gene PAX9 foi realizada utilizando-se o DNA genômico de 100 indivíduos afetados e 100 indivíduos controles. Após a obtenção e extração do DNA, as regiões de interesse foram amplificadas por reação em cadeia da polimerase (PCR) e os polimorfismos foram analisados por digestão com enzima de restrição. Os géis foram corados pelo nitrato de prata. A análise estatística foi realizada através das Simulações de Monte Carlo (programa Clump) e teste Qui-quadrado ao nível de significância de 5%. O programa ARLEQUIN foi utilizado para verificar combinações de haplótipos nos genes do TGF- BETA1 e PAX9. As análises mostraram que o polimorfismo da região promotora do TIMP2 não está presente na população estudada, que os polimorfismos na região promotora dos genes TGF BETA1 e MMP9 não estão associados com agenesia dental, e que os polimorfismos no promotor do PAX9 estão associados com a agenesia dental, podendo ser considerados marcadores genéticos para a hipodontia
Abstract: Hypodontia, the congenital absence of one or a few teeth, is one of the most common alterations of the human dentition. The most common permanent missing teeth are the third molars, maxillary second premolars and maxillary lateral incisors. Although hypodontia does not represent a serious public health problem, it may cause masticatory and speech dysfunctions and esthetic problems. TGFBETA1, MMP9, TIMP2 and PAX9 genes are expressed in many regions of the tooth germ during the diverse phases of odontogenesis. Recent studies show that polymorphisms in transcription regulator regions seem to be frequent and that these variations are responsible for individual phenotypic features. However, the role of genetic polymorphisms in the development of sporadic tooth agenesis is not established. The aim of this study was to analyse the association between TGF BETA1, MMP9, TIMP2 and PAX9 genes promoter polymorphisms and hypodontia in humans. Samples consisted of genomic DNA of 50 affected individuals and 50 control subjects, with age above 16. For PAX9 promoter polymorphisms analysis, test and control groups were composed of 100 individuals. After DNA extraction, the regions of interest were amplyfied by polymerase chain reaction (PCR). The polymorphic sites were analysed by restriction length fragment polymorphism (RLFP). The gel bands were stained by silver nitrate. Monte Carlo simulations (Clump software) and Chi-square test (x2) were used for statistical analysis. Differences were considered significant when p<0.05. ARLEQUIN computer program was used to analyse haplotypic combinations in TGF BETA1 and PAX9 genes. The analysis showed that TIMP2 promoter polymorphism was not present in the studied population and that TGF BETA1 and MMP9 promoter polymorphisms are not associated with hypodontia. There was a positive correlation between the two PAX9 promoter polymorphisms and hypodontia
Doutorado
Histologia e Embriologia
Doutor em Biologia Buco-Dental
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Phan, Alexandra. "Identification of MMP-9 as a Driving Factor in SARS-CoV-2 Entry." Thesis, Université d'Ottawa / University of Ottawa, 2021. http://hdl.handle.net/10393/42771.
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Since its emergence in December 2019, SARS-CoV-2 has infected over 200 million people globally. SARS-CoV-2 spike (S) decorates the viral envelope and is responsible for facilitating viral entry into the host cell. To mediate membrane fusion, S must be proteolytically cleaved. For the closely related SARS-CoV S, cleavage at the host cell surface must be facilitated by the serine protease TMPRSS2. We demonstrated that SARS-CoV-2 S can facilitate fusion independent of TMPRSS2 and sought to identify other proteases capable of driving SARS-CoV-2 S-mediated fusion. We show that the ADAMs and MMP inhibitor GI 254023X is capable of substantially reducing SARS-CoV-2 S-mediated syncytium formation. Additionally, we identified MMP-9, a protein target of GI 254023X, as a host protease capable of enhancing SARS-CoV-2 lentivirus entry in HEK293T-ACE2 cells. These results implicate ADAM and MMP proteases, in particular MMP-9, as potential antiviral drug targets against COVID-19 pathogenesis.
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CALLEGARI, E. M. R. "Estudo de Biomarcadores Relacionados à Agressividade e Invasividade em Lesões de Carcinoma de Células Escamosas Orais." Universidade Federal do Espírito Santo, 2015. http://repositorio.ufes.br/handle/10/8197.
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Previous issue date: 2015-11-20No processo de tumorigênese, a laminina-332 executa múltiplos processos biológicos através de sua cadeia γ2, e a MMP-9 atua no processamento dos componentes extracelulares. Nós propomos analisar o perfil molecular da cadeia γ2 e da MMP-9 em leucoplasias de alto risco, carcinomas in situ (CIS) e carcinomas de células escamosas invasivos (CCEs) e estabelecer possíveis correlações clinicopatológicas. As expressões da cadeia γ2 e de MMP-9 foram avaliadas por imunohistoquímica em 10 pacientes com lesões orais de alto risco de malignizaçāo e 26 casos com CCE invasivos. Através de imunomarcação da cadeia γ2 foi possível observar uma membrana basal contínua na maioria das lesões de alto risco de malignizaçāo enquanto que uma membrana descontínua ou ausente predominou nos casos de CCEs invasivos. Células do estroma de CCE invasivos apresentaram expressão mais elevada de MMP-9 quando comparada aos casos de lesões de alto risco. A associação entre o perfil clínico dos pacientes e os achados imunohistoquímicos demonstrou que fumantes com CCEs invasivos tiveram expressão mais elevada da cadeia γ2 no compartimento epitelial e de MMP-9 nos fronts invasivos. Ainda, aumento da expressão de MMP-9 no estroma foi associado aos pacientes do sexo masculino com idade superior a 60 anos diagnosticados com CCE invasivo. Nossos resultados indicam uma associação entre características clínicas e microscópicas em lesões orais com alto potencial de malignização e nos carcinomas orais, com uma mudança progressiva na expressão da cadeia γ2 e MMP-9 durante o processo de tumorigênese.
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Reis, Sabrina Thalita dos. "Análise da expressão de MMP-2, MMP-9, MT1-MMP (MMP-14), TIMP-1, TIMP-2, RECK, TGF-Beta e interleucina-8 em câncer de próstata." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5153/tde-22092011-133255/.
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Introdução: O câncer de próstata (CaP) é o tumor mais freqüente do homem no Brasil tendo sido estimados mais de 52.350 novos casos em 2010, sendo a segunda causa de óbito por câncer em homens. O prognóstico depende fundamentalmente dos níveis séricos de Prostatic Specific Antigen (PSA) estádio tumoral (TNM) e grau de diferenciação histológica (Gleason). Porém esses têm sido insuficientes na definição do prognóstico da neoplasia. Por isso pesquisas têm sido direcionadas para a identificação de alterações moleculares que possam prever o potencial de agressividade do câncer de próstata. Metaloproteinases da matriz (MMP) são proteínas pertencentes a uma família de aproximadamente 30 enzimas proteolíticas ou endoproteinases que degradam vários componentes da matriz extracelular. A detecção de sua expressão tem sido estudada como marcador sensível e específico de vários tumores, principalmente as MMP pertencentes ao grupo das gelatinases MMP-2 e MMP-9. Objetivo: o objetivo deste nosso trabalho foi avaliarmos pela técnica de qRT-PCR e imuno-histoquímica os níveis de expressão dos genes das MMP pertencentes ao grupo das gelatinases, MMP-2 e MMP-9, bem como outros sabidamente envolvidos em suas vias de ativação (MMP-14, IL-8) e inibição (TIMP-1, TIMP-2, RECK e TGF-) no câncer localizado de próstata. Material e Métodos: O estudo consistiu na análise de espécimes de 79 pacientes com câncer da próstata submetidos a prostatectomia radical entre setembro de 1997 e fevereiro de 2000. Esses oito genes foram então testados quanto a seu valor prognóstico no câncer da próstata através da técnica de reação em cadeia da polimerase quantitativa com transcriptase reversa (qRT-PCR). Análise proteica foi feita a partir de 40 pacientes deste pool. O grupo controle foi composto de tecido de 11 pacientes com hiperplasia benigna da próstata (HPB) tratados cirurgicamente com prostatectomia retropúbica. Resultados: MMP-9 esteve superexpressa e MMP-2, TIMP-1, TIMP-2, MMP 14, IL-8, TGF- e RECK se mostraram subexpressos em tecido representativo de CaP quando comparado com HPB. A análise dos níveis de expressão dos genes com o escore de Gleason, mostrou que MMP-2 e TIMP-2 mesmo mantendo-se subexpressos, tiveram uma expressão maior entre os pacientes que apresentavam Gleason 7 (p=0,04 e p=0,02 respectivamente). De acordo com o valor de PSA préoperatório, encontramos diferenças na expressão de MMP-9. Pacientes que apresentavam um PSA pré-operatório 10 ng/mL possuíam uma mediana de expressão maior que aqueles cujo PSA pré-operatório <10 ng/mL com medianas de expressão de 5,62 e 2,76 respectivamente (p=0,033). Não encontramos diferenças estatísticas entre pacientes que apresentavam ou não recidiva bioquímica quanto a expressão dos 8 genes estudados. Porém o gene da MMP-9 apresentou uma diferença estatística marginal apresentando uma mediana de expressão de 6,29x nos pacientes que apresentaram recidiva bioquímica e de 3,25 nos pacientes que não apresentaram recidiva bioquímica (p=0,090). De acordo com a expressão proteica, encontramos uma maior positividade em MMP-9, MMP-2, TGF-, IL-8 e MMP-14. De acordo com os fatores prognósticos encontramos associação de TIMP-1 com recidiva bioquímica. Conclusão: Encontramos uma superexpressão de MMP-9 e uma subexpressão de MMP-2, TIMP-1, TIMP-2, MMP-14, RECK, IL-8 e TGF- no CaP. Considerando os fatores prognósticos encontramos que aumentados níveis de expressão do gene da MMP-9 associou-se a aumentados níveis de PSA, e mostrou uma tendência de associação com recidiva bioquímica. De acordo com a expressão proteica encontramos que a ausência de TIMP-1 pode ser um indicativo de recidiva bioquímicaIntroduction: Currently, Prostate cancer (PCa) is the most common tumor in men in Brazil. It was estimated that more than 52,350 new cases were diagnosed in 2010, being the second cause of death by cancer in man. The prognosis depends mainly on Prostate Specific Antigen (PSA) serum levels, tumor stage (TNM) and histological grade (Gleason), but these parameters, even combined, are insufficient to define the correct prognosis of PCa. Therefore research has been directed towards the identification of molecular alterations that may predict potential aggressiveness of PCa. Matrix metalloproteinases (MMPs) are proteins that belong to a family of about 30 proteolytic enzymes that degrade various components of the extracellular matrix. The analysis of MMPs expression has been studied as a sensitive and specific marker of prognosis of several tumors, and special attention was focused in the group of gelatinases, MMP-2 and MMP-9.Objective: The aim of this study was to evaluate the expression levels of MMP-2 and MMP-9 genes and proteins by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry in localized PCa. We also evaluated the expression of genes that are involved in the control of MMP-2 and MMP as activators (MMP- 14, IL-8) or inhibitors (TIMP-1, TIMP-2, RECK and TGF-).Materials and Methods: The casuistic consisted of 79 surgical specimens from patients with localized PCa who underwent radical prostatectomy between September 1997 and February 2000. The control group was composed of specimens from 11 patients with benign prostatic hyperplasia (BPH) treated surgically with retropubic prostatectomy. The results of the 8 genes expression, through qRTPCR and immunohistochemistry, were correlated to the diagnosis and prognosis of PCa. The protein expression analysis was carried out in 40 patients of the casuistic. Results: The MMP-9 was overexpressed, while MMP-2, TIMP-1, TIMP-2, MMP-14, RECK, IL-8, and TGF- were underexpressed in malignant prostate tissue compared to BPH. Patients with Gleason7 had higher expression of MMP-2 and TIMP-2 (p=0.04, p=0.02 respectively). According to the preoperative PSA value, we found that patients with preoperative PSA10 ng/mL had a median of expression of 5.62 compared to 2.76 when PSA<10 ng/mL (p=0.033). There were no statistical differences between expression of the eight genes and biochemical recurrence during follow up. However, the higher MMP-9 expression was marginally associated with recurrence, the median was of 6.29 in recurrence patients compared to 3.25 in those without recurrence (p=0.090). Regarding the protein expression, we found a higher positivity of MMP-9, MMP-2, TGF-, IL-8 e MMP-14 expression in PCa, and a correlation between the lack of TIMP-1 and tumor recurrence. Conclusion: MMP-9 is overexpressed while MMP-2, TIMP-1, TIMP-2, MMP-14, RECK, TGF- and IL-8 are underexpressed in CaP. According to the prognostic factors, we observed that increased level of MMP-9 was associated with pre-surgical PSA10 ng/mL. Also there was a tendency of association between higher MMP- 9 expression and biochemical recurrence. Overexpression of MMP-9 can be explained by the underexpression of their major inhibitors TIMP-1 and RECK. According to protein expression we found that absence of TIMP-1 is correlated with biochemical recurrence in the PCa
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Heinrich, Roxana. "Befristung und Bedingung baulicher und sonstiger Nutzungsrechte nach [section] 9 Abs. 2 BauGB /." Frankfurt am Main : Lang, Peter Frankfurt, 2009. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=017717535&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
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Olofsson, Rebecka, and Josefine Yngvesson. "Barns tankar om begreppet hälsa - en intervjustudie med 9 elever i skolår 2." Thesis, Kristianstad University College, Department of Teacher Education, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:hkr:diva-3974.
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Syftet med examensarbetet är att visa hur barn tänker om begreppet hälsa och hur man kan använda tematiskt arbete för att utveckla deras tankar. I teorigenomgången redogörs olika definitioner av hälsa, läroplanerna och hur barn tänker och lär. Metoden har varit intervjuer med hjälp av tankekartor och intervjufrågor. Nio elever i skolår 2 har intervjuats vid två tillfällen. Den första intervjun skedde före temaarbetets start och den andra intervjun skedde efteråt. Temat om hälsa varade i fyra veckor, då vi använde oss av definitionen må bra i samband med hälsa. Vid första intervjutillfället konstaterades att eleverna inte hade så många tankar kring hälsa, dessa utvecklades dock efter temaarbetet. Eleverna hade då skapat sig en större helhetsbild av hälsa som bland annat innefattade tankar om mat, vila och rörelse. De hade även insikt om vikten av vänskap för att må bra.
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Röpke, Melanie [Verfasser]. "Die Gestaltbarkeit von Arbeitsbedingungen im Rahmen von § 9 Nr. 2 AÜG / Melanie Röpke." Baden-Baden : Nomos Verlagsgesellschaft mbH & Co. KG, 2016. http://d-nb.info/1106280156/34.
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Salonurmi, T. (Tuire). "Cell lineage specific expression of matrix metalloproteinases -2 and -9 in transgenic mice." Doctoral thesis, University of Oulu, 2004. http://urn.fi/urn:isbn:9514273540.
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Abstract
Mammalian extracellular matrix metalloproteinases, MMPs, are a family of enzymes capable of degrading components of the connective tissue. The in vivo regulation of the cell lineage-specific expression of MMPs, however, is not well known. This study used transgenic mice to identify cell-specific elements in the upstream regulatory regions of MMP-2 and MMP-9. Transgenic mice were generated by pronuclear microinjections into fertilised oocytes using lacZ as a reporter gene. The reporter gene constructs containing varying lengths of the MMP-9 5'-upstream region revealed an area that allowed for expression in osteoclasts and migrating keratinocytes, the cells that also express MMP-9 in vivo. The sequence driving the cell specific expression included the nucleotides from -2722 to -7745.
When the same upstream regulatory fragment of MMP-9 was used to drive the expression of the human tissue specific inhibitor of MMPs, TIMP-1, instead of lacZ, the transgenic mice developed normally and the animals were fertile with normal post-embryonic growth. However, cutaneous wound healing was remarkably retarded, but not totally prevented, and the migration of keratinocytes over the wound was slow. The mice expressed the human TIMP-1 in keratinocytes during wound healing and in situ zymography revealed a total blockage of the gelatinolytic activity of MMP-2 and MMP-9, the main gelatinases active in the healing wound tissues.
By using a sequence of 6500 base pairs from the 5'-upstream regulatory region of the MMP-2 gene it was possible to drive the expression of lacZ in mesenchymal cells of the developing transgenic mouse embryo. The expression pattern was similar to that found in previous in situ hybridization studies, following the different stages of tissue morphogenesis and being present in the areas of basement membrane degradation and epithelial cell invasion. Computer analyses of the sequence revealed three regulatory upstream regions conserved between human, mouse, and rat, and possibly responsible for the cell-and tissue specificity. New transgene constructs containing fragments of the conserved regions will provide a more detailed profile of the in vivo MMP-2 regulation in the future.
This study defined a fragment in the upstream regulatory region of MMP-9 that is essential for expression in osteoclasts and migrating keratinocytes. Furthermore, the keratinocyte derived MMPs, including MMP-9, were found to play important role in epithelial cell migration in the area of the healing wound.
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Silva, Sheila Nogueira Saraiva da [UNESP]. "Metaloproteinases da matriz 2 e 9 em coelhos com cardiomiopatia induzida pela doxorrubicina." Universidade Estadual Paulista (UNESP), 2014. http://hdl.handle.net/11449/121883.
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000814074.pdf: 683274 bytes, checksum: 7aed95862bef3ef98072762605457374 (MD5)A doxorrubicina é um quimioterápico bastante utilizado em pacientes oncológicos e sua cardiotoxicidade está relacionada com vários mecanismos celulares, incluindo necrose e apoptose. Estudos têm aventado a participação das metaloproteinases da matriz e seus inibidores na cardiotoxicidade induzida pela doxorrubicina. Assim, esta pesquisa teve como objetivo avaliar as atividades plasmática e miocárdica das metaloproteinases da matriz 2 e 9 em coelhos com cardiomiopatia por doxorrubicina, correlacionando-as com o remodelamento cardíaco que acompanha tal enfermidade. Os animais foram divididos em dois grupos: controle (n=10) e doxorrubicina (n=15). As atividades plasmática e miocárdica foram analisadas através do método de zimografia. Foram evidenciadas apenas as formas inativas das MMPs (pro-MMP) nas amostras sanguíneas analisadas. A pro-MMP-2 foi documentada no plasma dos animais controle e daqueles com cardiomiopatia por doxorrubicina em todos os momentos de avaliação. Já a pro-MMP-9 foi encontrada em algumas amostras dos grupos controle e enfermo, principalmente nos momentos de valiação T30 e T45, porém em fraca marcação. Houve diferença significativa na atividade das pro-MMPs-2 e 9 ao longo dos tempos de estudo. Os testes de correlação entre as pro-MMPs plasmática e os parâmetros ecocardiográficos evidenciaram resultados significativos. Em T0 verificou-se correlação entre A’lat e pro-MMP-2; em T15 documentaram-se correlações entre a pro-MMP-2 e os parâmetros PPE e TEI; já em T30 constatou-se correlação entre pro-MMP-9 e PLVE%; em T45, finalmente, foram observadas correlações entre pro-MMP-2 e os parâmetros DIVEs, DIVEd, SIVs e Emitral/E’sep, assim como entre pro-MMP-9 e TEVE. No miocárdio evidenciou-se apenas a pro-MMP-2. A atividade plasmática das MMPs, em especial a pro-MMP 2, pôde ser relacionada às alterações morfofuncionais da cardiomiopatia induzida, sendo que não houve correlação ...
Doxorubicin is a chemotherapy agent frequently used in oncology patients. Its cardiotoxicity is related to several cellular mechanisms, including necrosis and apoptosis. Some studies have ascribed a role to matrix metalloproteinases and their inhibitors in the cardiotoxicity induced by doxorubicin. Therefore, this research was aimed at evaluating the plasma and myocardial activities of matrix metalloproteinases 2 and 9 in rabbits with doxorubicin-induced cardiomyopathy, searching for a correlation between them and the cardiac remodeling attributable to such disease. The animals were assigned into two groups: control (n=10) and doxorubicin (n=15). The plasmatic and myocardial activities were analyzed through the method of zymography. Only the inactive MMPs (pro-MMP) have been identified in the blood samples. The plasma pro-MMP-2 was documented in both control and doxurubicin animals from T0 to T45. On the contrary, the pro-MMP-9 was found in some samples of control and doxurubicin groups, especially at T30 and T45, although only weak bands have been demonstrated. A significant difference was shown to occur in pro-MMPs-2 and 9 along time. Correlation tests between the plasma pro-MMPs and the echocardiographic data demonstrated significant results. At T0 a correlation was found between A’lat and pro-MMP-2; at T15 correlations were documented between pro-MMP-2 and the parameters PEP and TEI; at T30 a correlation was identified between pro-MMP-9 and PLVE%; lastly, at T45 correlations have been observed between pro-MMP-2 and the parameters LVIDs, LVIDd, IVSs e Emitral/E’sep, as well as between pro-MMP-9 and LVET. Only the pro-MMP-2 was documented at the myocardium, although no significant difference between groups could be demonstrated. The plasmatic activity of the MMPs, specially the pro-MMP2, could be related to the morphofunctional alterations of the induced cardiomyopathy, and that there was no correlation between the plasmatic ...